Medical device including unitary, continuous portion of varying durometer

ABSTRACT

A medical device ( 110 ) including a catheter shaft ( 111 ) and a unitarily and continuously formed portion ( 108 ) having a varying durometer, and optionally including an expandable balloon ( 18, 118 ). One or both of the unitarily and continuously formed portion ( 108 ) and the balloon ( 18, 118 ) are made from an irradiation cross-linked or cross-linkable mixture of a polyamide elastomer and at least one additional cross-linking reactant. The polyamide elastomer can be a polyester amide, a polyether ester amide or a polyether amide, and is preferably a nylon block copolymer. The aromatic molecule can be 1,3,5 triethyl benzene; 1,2,4 triethyl benzene; and 1,3,5 triisopropyl benzene. The cross-linking reactant can be: (a) a difunctional material, (b) a trifunctional material, (c) a tetrafunctional material, or (d) an aromatic molecule containing at least two ring substituents, each of the ring substituents having labile hydrogens at a benzylic site therein. The cross-linking reactant can also be diallyl phthalate or meta-phenylene dimaleimide.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a Divisional Patent Application of patent application Ser. No.09/848,742, filed May 3, 2001, now U.S. Pat. No. 6,881,209 which isbased on patent application Ser. No. 09/663,747, filed Sep. 15, 2000 andalso claims priority of U.S. Provisional Patent Application Ser. No.60/207,058 filed May 25, 2000.

FIELD OF THE INVENTION

This invention relates generally to medical devices such as devices fordeploying another medical device such as a stent into a patient; ordevices which are themselves to be introduced into a patient, forexample, for establishing a passage or lumen in a patient, for expandinga narrowed or obstructed passage or lumen in a patient or forintroducing a therapeutic or diagnostic fluid into a patient.

BACKGROUND OF THE INVENTION

Medical devices which incorporate inflatable or expandable balloonsserve a wide variety of purposes. The balloon is carried on or affixedto a catheter shaft for delivery of the balloon to a desired location inthe patient. The catheter shaft includes a lumen for introducing aninflation fluid into the balloon. For example, such catheter balloonsare widely known to be useful for performing angioplasty procedures orthe like, in which narrowings or obstructions in blood vessels or otherbody passageways are altered in order to increase blood flow through thenarrow or obstructed area. More specifically, in a typical balloonangioplasty procedure, a balloon catheter is percutaneously introducedinto the patient by way of the arterial system and advanced until theballoon of the catheter lies across the vascular narrowing orobstruction. The balloon is then inflated to dilate the vessel lumen atthe site of the narrowing or obstruction. If desired, a stent may bepositioned over the balloon and deployed at the site of the narrowing orobstruction to ensure that the dilated vessel lumen remains open.Balloon catheters find utility in a wide range of procedures, includingvalvuloplasty and urological procedures, among others.

The balloons of prior balloon catheters have been constructed from awide variety of polymeric materials. These balloons each have their ownadvantages and drawbacks. Balloons comprising polyethylene terephthalate(PET), for example, have a relatively low degree of distention orexpansion once they are inflated. This generally minimizes any potentialadverse effects from overinflation or overexpansion of the balloon orany stent carried on it. Semi-distending or non-distending balloonsoften possess relatively high tensile strength, burst pressure andpuncture resistance, qualities highly desirable for dilating toughlesions or for deploying and expanding stents carried over them.

However, body vessels such as arteries are generally tapered, and thelocations at which narrowings or obstructions may occur vary, so that aballoon which closely matches the ultimately desired diameter of thevessel may not be readily available. Moreover, it may at times bedesirable to be able to increase the diameter of the balloon beyond thatwhich had been contemplated before the balloon procedure was begun.While balloons comprising materials such as polyvinyl chloride can bemore distensible than PET or the like, balloons comprising suchmaterials often possess a significantly lower tensile strength, burstpressure or puncture resistance than the less-distensible balloons.Overinflation of such balloons is also possible.

A variety of attempts have been made to construct medical deviceballoons from materials which yield balloons of good strength (that is,relatively high tensile strength and burst pressure, and good punctureresistance) while retaining an adequate degree of compliance, that is,an acceptable ratio of balloon diameter growth under an applied pressureto that balloon pressure. Each of these attempts possesses its ownadvantages and disadvantages. Balloons made from materials such as PETmay possess excessive crystallinity or may be too stiff, so that suchballoons may be resistant to the folding desired to minimize the profileof the catheter in which the balloon is employed; such resistance tofolding is particularly problematic when the balloon is deflatedfollowing inflation during an in situ application, in order to beretracted into the distal end of the catheter for withdrawal. A minimalcatheter profile is a highly desirable characteristic of ballooncatheters, however. Some materials do not readily accept coating withdrugs or lubricants, and some materials are difficult to fuse or adhereto conventional catheter shafts. Balloons made of some biaxiallyoriented nylons or polyamides have been asserted to overcome some ofthese problems.

Catheter balloons comprised of block copolymers have been suggested as away of achieving an acceptable combination of balloon strength andelasticity. For example, it is known that catheter balloons can beconstructed from polyamide/polyether block copolymers, commonlyidentified by the acronym PEBA (polyether block amide). Many of suchcopolymers can be characterized by a two phase structure, one being athermoplastic region that is primarily a polyamide, semicrystalline atroom temperature, and the other being an elastomer region that is richin polyether. Balloons comprising such copolymers are asserted topossess a desirable combination of strength, compliance and softness.Catheter balloons comprising blends of two or more such copolymers arealso known, and it has been asserted that irradiating such blends canenhance the properties of the resulting balloons, including increasedburst pressures.

It would be highly advantageous to have medical devices which includedexpandable or inflatable balloons with improved strength, for example,with greater tensile strength, burst pressure and/or punctureresistance, while simultaneously possessing acceptable compliance (inthis case, an acceptable ratio of balloon diameter growth to balloonpressure). It would also be highly advantageous to have medical devicesmade from materials which meet a variety of desirable processingcriteria, including thermal stability, non-toxicity, non-volatility,high boiling point (preferably, solid at room temperature), high flashpoint, insensitivity to moisture and commercial availability.

It would also be advantageous to have balloon-type or other medicaldevices (such as catheters) which had a varying durometer or durometerhardness, that is, a varying resistance to deformation upon theapplication of a transverse force, but which did not need to beconstructed from multiple pieces of different durometers. “Durometer” or“durometer hardness” usually refers to the resistance of materials suchas rubber or plastics to deformation, typically to deformation by anindenter of specific size and shape under a known load. The stiffness orresistance to lateral deformation of an elongate rubber, plastic orportion of a medical device often correlates to durometer hardness, asdoes balloon burst pressure. The stiffness or resistance to lateraldeformation of such an elongate portion also often correlates to themodulus of elasticity or flexural modulus of the rubber, plastic orother material of which the elongate portion is made. For brevity, theuse of the phrase “varying durometer” herein refers to changes in any orall of durometer hardness, stiffness, resistance to lateral deformation,modulus of elasticity, flexural modulus or other desirable functionalproperty. Use of the word “durometer” herein is therefore not limited todurometer hardness or to properties which correlate to durometerhardness. As used herein, “durometer” instead also includes propertiessuch as modulus of elasticity and flexural modulus which do notnecessarily correlate to durometer hardness, since materials having thesame durometer hardness may have different moduli of elasticity ordifferent flexural moduli, and thus different stiffnesses.

Varying durometer along the length of a medical device enables differentparts of a device to perform different functions. Unfortunately, presentmethods or structures for achieving a variable durometer along thelength of a catheter shaft or other medical device entail securing twoor more separate pieces of different durometer by adhesion, heatbonding, butt bonding, sonic welding, mechanical means or the like. Theresulting structures have a very rapid or abrupt change in composition,and therefore a very rapid or abrupt change in durometer, at thejunction of the pieces of different durometer. One drawback of suchstructures is that the very rapid or abrupt change in durometer createsa kink point at which the catheter shaft or the like is subject tofolding over during use, making the catheter shaft or the like moredifficult to advance in the patient. Eliminating this abrupt change incomposition while allowing the medical device (or portion thereof) tohave different durometers along its length would make it easier toadvance a catheter shaft or the like in a patient. Moreover,particularly in devices having very small cross-sectional diameters, itis often difficult to reliably secure together different pieces of verysmall diameter. This difficulty would be avoided if the different piecesof the medical devices could be continuously formed. It would further beadvantageous to achieve a varying durometer without the need for heatbonding two or more separate pieces, as heat bonding the pieces addsheat history to them, along with an associated risk of degradation atthe bond site. It would also be advantageous to have medical devices inwhich a change in durometer was gradual over an appreciable length ofthe devices, that is, over a length long enough to improve the practicalutility of such devices, such as by obviating kinking or the like.

BRIEF SUMMARY OF THE INVENTION

Many of the foregoing problems are solved and a technical advance isachieved in an illustrative medical device for positioning an includedballoon within a human or veterinary patient, for example, for deployinganother medical device such as a stent in the patient or for expanding apassage or lumen in the patient. More particularly, in a first preferredembodiment, the medical device of the present invention comprises acatheter shaft and an expandable balloon carried by the catheter shaft.The medical device of the present invention is characterized in that theballoon comprises an irradiation cross-linked mixture of a polyamideelastomer and at least one additional cross-linking reactant.

This additional cross-linking reactant performs a role which is quitedifferent from that performed by the two reaction promoters disclosed inInternational Application WO 98/55171. That Application is directed to across-linked nylon block copolymer which comprises an irradiationcross-linked copolymer containing a polyamide block and an elastomericblock, including a compound which promotes cross-linking therein. Theprocess disclosed in that application comprises supplying the nylonblock copolymer with a cross-linking “promotoer” (sic.) and exposing theblock copolymer to irradiation sufficient to cross-link the copolymer.Only two promoters are disclosed, triallylcyanurate andtriallylisocyanurate, at 2 percent by weight in PEBAX® brand nylon blockcopolymer (Atochem, Inc., brand of polymers consisting of polyetherblocks separated by polyamide blocks). Irradiation is carried out at 5to 20 megarads (no specific type of irradiation is disclosed), althoughthe Application points out that degradation of the material may takeplace when total irradiation becomes too high, for example, at 15 or 20megarads. That Application claims (among others) an improvement in aballoon type catheter having a tubular shaft comprising a nylon blockcopolymer and an integrally formed balloon section, the improvementcomprising irradiation crosslinking the copolymer of the balloonsection, wherein the crosslinking lowers the percent elongation of theballoon section as compared to the elongation prior to crosslinking. Theonly apparent support in the specification for that claim appears to bea single statement that, in the case of balloon catheters manufacturedfrom a nylon block copolymer, the invention therein provides for thepreparation of a balloon type catheter wherein the balloon sectionrelative to the shaft can be converted into a thermoset or crosslinkedtype structure, thereby increasing its overall mechanical strength,performance, and durability. That Application appears to make no otherdisclosure of any process whatsoever for manufacturing such a balloon,and appears to contain absolutely no details as to how such a processcould or should be carried out.

The present invention is quite distinct; the cross-linking reactant ofthe present invention and the promoter of that Application appear to actin different ways to perform different functions. “Promoter” is awell-recognized term of art, of course, referring to a material whichenhances the activity of a catalyst. More particularly, a promoter is asubstance that, when added in relatively small quantities to a catalyst,increases its activity; Lewis, Sr., Hawley's Condensed ChemicalDictionary 12th (Van Nostrand Reinhold Company, New York, N.Y., 1993)(definition 1), at 966; or is a chemical which itself is a feeblecatalyst, but greatly increases the activity of a given catalyst;Parker, McGraw-Hill Dictionary of Scientific and Technical Terms 5th(McGraw-Hill, Inc., New York, N.Y., 1994) (first definition), at 1589.Catalysts, of course, accelerate or retard the velocity of a chemicalreaction without being consumed during the course of those reactions.They do not become incorporated into the chemical structures of theproducts of the reactions, and in theory can be recovered at the end ofthe reaction essentially unaltered in form and amount (even though inpractice they might be retained in the physical object constituted bythe reaction products). This is presumably true of the two materialsmentioned in that Application, since they appear to be solely describedin that Application as “promoters.” While it might be argued whetherenergy should properly be called a catalyst, it is believed that the useof the word “promoters” in that Application would be readily understoodby those in the medical device field to refer to materials whichincreased the activity of the irradiation employed in that Application,that is, increased irradiation cross-linking between the chainsthemselves of the nylon block copolymer it discloses.

In direct contrast to any balloon or medical device containing the twospecific promoters of that Application at their disclosedconcentrations, the medical device of the present invention comprises aballoon in which one or more specific cross-linking reactants are, byirradiation, chemically incorporated into the polyamide elastomer withwhich they are initially mixed. Thus, where the two promoters of thatApplication would cause the various chains within the polyamideelastomer of any balloon to cross-link directly to one another, thespecific cross-linking reactants in the balloon of the present inventioninstead themselves form and constitute links or bridges between thevarious chains within the polyamide elastomer. Thus, the molecularstructure and physical properties of the balloon incorporated in themedical device of the present invention are different from those whichmight be expected to be possessed by a balloon which included either ofthe two catalysts or promoters of that Application.

The particular cross-linking reactants useful in the medical device ofthe present invention, and in particular, in the balloon thereof, areexpected to include difunctional materials such as diallyl adipate;diallyl carbonate; diallyl maleate; diallyl succinate; diallyltetrabromophthalate; diethyl diallylmalonate; dimethyl diallylmalonate;and 2,2,6,6-tetrabromobisphenol A diallyl ether. Useful cross-linkingreactants are also expected to include trifunctional materials such as2,5-diallyl-4,5-dimethyl-2-cyclopenten-1-one; diallyl fumarate; diallylitaconate; 1,3,5-triallyl-2-methoxybenzene; triallyl trimesate (triallyl1,3,5-benzenetricarboxylate); triallyl trimellitate (triallyl1,2,4-benzenetricarboxylate); and pentaerythritol triallyl ether; andtetrafunctional materials such as tetraallylcis,cis,cis,cis-cyclopentane-1,2,3,4-tetracarboxylate; andN,N,N′,N′-tetraallylethylenediamine. Useful materials are also expectedto include aromatic molecules containing at least two ring substituents,each of the ring substituents having labile hydrogens at a benzylic sitetherein. 1,3,5 triethyl benzene; 1,2,4 triethyl benzene; and 1,3,5triisopropyl benzene are commercially available examples of sucharomatic molecules containing at least two substituents having labilehydrogens at a benzylic site. Useful materials are further expected toinclude diallyl phthalate and meta-phenylene dimaleimide; these lattertwo constitute a second preferred embodiment of the present invention.

All of these materials are expected to possess at least several of avariety of desirable characteristics for manufacturing the medicaldevice of the present invention: thermal stability, non-toxicity,non-volatility, high boiling point (preferably, solid at roomtemperature), high flash point, insensitivity to moisture and commercialavailability. However, not all of these materials possess all of thesedesirable characteristics. Other materials capable of forming allylic orbenzylic radicals having comparable reactivity should be useful as well.The primary criteria for selecting such other materials may be that theyare less reactive than species such as epoxies, methacrylates andacrylates; and that they are relatively “small” molecules, that is, theyare small enough to fit between (and thereby be capable ofcross-linking) the various chains of the particular polyamide elastomerbeing used. The materials must of course be multifunctional, to be ableto cross-link to at least two of those chains.

The more reactive species such as epoxies, methacrylates and acrylatesare probably undesirable for use in the medical device of the presentinvention because they are likely to cross-link the polyamide elastomertoo rapidly, completing the cross-linking reaction during preliminarythermal processing of the polyamide elastomer (prior to its being formedinto the balloon of the device). Such premature cross-linking clogs theprocessing equipment, such that completion of the balloon-formingprocess is impossible. Multifunctional allylic materials are more stableand less reactive than these, so that they readily survive thermalprocessing but are still reactive enough when exposed to a source ofenergy to achieve good cross-linking.

The allylic radical and the benzylic radical differ in bond dissociationenergies (and hence radical stabilities and reactivities) by only 2kcal/mol (7 kJ/mol); J. March, Advanced Organic Chemistry 4th, at 191(John Wiley & Sons, New York, N.Y., 1992). Accordingly, a wide varietyof multifunctional benzylic small molecules are expected to be useful inthe medical device of the present invention; the three listed above havethe advantage of being commercially available at the present time. Theselection of other materials having suitably positioned labile hydrogensshould be well within the level of skill in the field of designingmedical devices of this type, since the recognition of labile hydrogenpositions is generally taught quite early in introductory (collegesophomore) organic chemistry.

While some modest degree of trial-by-error experimentation may be neededto confirm the practical utility of any particular allylic or benzylicmaterial contemplated for use in the present invention but notspecifically disclosed herein, such experimentation is not believed tobe undue under the circumstances, but is instead believed to besubstantially below the amount of testing that would be required forregulatory approval for actually marketing a medical deviceincorporating a balloon comprising such a particular material as across-linking reactant.

While attempting to manufacture a medical device balloon employing thetwo promoters disclosed in International Application WO 98/55171, it wasdiscovered that these two specific materials could in fact act ascross-linking reactants (instead of merely augmenting the cross-linkingactivity of the disclosed irradiation) under concentrations orconditions other than the concentrations or conditions disclosed in thatApplication. More particularly, attempts to make a parison for forming amedical device balloon from a mixture of PEBAX® brand nylon blockcopolymer with 2 percent by weight of one of those materials weregenerally unsuccessful or unacceptable for commercial purposes, due tothe significant formation of gelling in the parison. “Gelling” is a termof art which indicates the formation of small, discrete volumes, areas,particles or particulates which are a result of premature, undesirablethermal cross-linking of the copolymer or other polyamide elastomeritself. “Gelling” also includes other defects arising during themanufacture of the copolymer or other polyamide elastomer. Gelling inthe particular mixture under consideration prevented the successful useof the resulting parison to form a balloon for commercial purposes.

Since that Application teaches that higher levels of irradiation areundesirable, it is believed that those skilled in the field would haveconcluded that the only alternative left for improving the amount ofcross-linking would have been to increase the amount of promoter mixedwith the copolymer. Efforts in this direction were unsuccessful.Unexpectedly, it was found that an acceptable balloon could be obtainedby lowering, not increasing, the amount of the promoter. As a result,gelling was decreased to an acceptable level. It was found that at theselower levels the so-called “promoter” itself acted as a cross-linkingreactant, incorporated in the structure of the cross-linked copolymerbetween the chains of the copolymer. Such a result appears to bedirectly contrary to any reasonable expectation from the disclosure ofthat Application.

Accordingly, in a third preferred embodiment, the medical device of thepresent invention comprises a combination which is comparable to thefirst preferred embodiment, but which is instead characterized in thatits balloon is formed from an irradiated mixture of a polyamideelastomer and no more than about 1.5 percent by weight of eithertriallyl cyanurate or triallyl isocyanurate. It is believed that thesetwo materials advantageously possess most or all of the desirablecharacteristics mentioned above.

In all of these embodiments of the present invention, the polyamideelastomer can be one or more members of any of the three generallyrecognized families of polyamide elastomers: polyester amides (orPESAs), polyether ester amides (PEEAs) or polyether amides (PETAs).Representative PESAs include ESTAMID® brand polymer from Dow ChemicalCompany. Representative PEEAs include PEBAX® brand nylon blockcopolymer, VESTAMID® brand polymer from Creanova Corporation andGRILAMID®) brand polymer from Esmer Corporation. Representative PETAsinclude GRILON® brand polymer, also from Esmer Corporation.

Other preferred embodiments of the present invention described in moredetail below include the processes by which these three embodiments ofthe medical device of the present invention are assembled. The medicaldevice of the present invention may be particularly advantageous in thatthe puncture resistance, strength and burst pressure of its balloon maybe improved with respect to comparable irradiation cross-linked balloonslacking any cross-linking reactant.

In a first aspect, then, the present invention is directed to a medicaldevice comprising: a catheter shaft; and an expandable balloon carriedby the catheter shaft; wherein the balloon comprises an irradiationcross-linked mixture of a polyamide elastomer and at least oneadditional cross-linking reactant, the cross-linking reactantcomprising: (a) a difunctional material selected from the classconsisting of diallyl adipate; diallyl carbonate; diallyl maleate;diallyl succinate; diallyl tetrabromophthalate; diethyl diallylmalonate;dimethyl diallylmalonate; and 2,2,6,6-tetrabromobisphenol A diallylether; (b) a trifunctional material selected from the class consistingof 2,5-diallyl-4,5-dimethyl-2-cyclopenten-1-one; diallyl fumarate;diallyl itaconate; 1,3,5-triallyl-2-methoxybenzene; triallyl trimesate(triallyl 1,3,5-benzenetricarboxylate); triallyl trimellitate (triallyl1,2,4-benzenetricarboxylate); and pentaerythritol triallyl ether; (c) atetrafunctional material selected from the class consisting oftetraallyl cis,cis,cis,cis-cyclopentane-1,2,3,4-tetracarboxylate; andN,N,N′,N′-tetraallylethylenediamine; or (d) an aromatic moleculecontaining at least two ring substituents, each of the ring substituentshaving labile hydrogens at a benzylic site therein. In a second aspect,the present invention is directed to such a device in which the at leastone additional cross-linking agent comprises diallyl phthalate ormeta-phenylene dimaleimide.

The balloon of the medical device preferably comprises an amount of thecross-linking reactant sufficient to give the balloon a strengthgenerally about equal to and perhaps in some cases greater than that ofa balloon composed of the polyamide elastomer and comparablycross-linked by irradiation, but in the absence of any cross-linkingreactant, agent or promoter. The balloon more preferably comprises about1 to about 2 percent by weight of the difunctional material; about 0.5to about 1.5 percent by weight of the trifunctional material or thearomatic molecule containing at least two ring substituents, each of thering substituents having labile hydrogens at a benzylic site therein; orabout 0.01 to about 1 percent by weight of the tetrafunctional material.The balloon alternatively comprises about 1 to about 2 percent by weightdiallyl phthalate or meta-phenylene dimaleimide.

The balloon of the medical device further preferably comprises a mixtureof the polyamide elastomer and the cross-linking reactant which has beencross-linked by irradiation with an electron beam or with ultraviolet,X- or gamma rays. More preferably, the balloon comprises a mixture ofthe polyamide elastomer and the cross-linking reactant which has beencross-linked by exposure to about 0.5 to about 20 megarads of radiation.It is preferred that the balloon is formed by inflation of the mixtureof the polyamide elastomer and the cross-linking reactant after themixture has been cross-linked by irradiation.

As indicated above, the balloon of the medical device can comprise anymember of the polyamide elastomer families, such as polyester amides,polyether ester amides or polyether amides. The balloon preferablycomprises a nylon block copolymer including polyamide blocks separatedby elastomeric polyether blocks or segments. Suitable nylon blockcopolymers of this type are sold under the trademark PEBAX® by Atochem,Inc. Useful nylon block copolymers can instead include polyamide blocksseparated by other elastomeric blocks or segments, such as polyesters,hydrocarbons or polysiloxanes.

When the balloon comprises an irradiation cross-linked mixture of apolyamide elastomer and an aromatic molecule, it is preferred that thearomatic molecule containing at least two ring substituents, each of thering substituents having labile hydrogens at a benzylic site therein, isselected from the class consisting of 1,3,5 triethyl benzene; 1,2,4triethyl benzene; and 1,3,5 triisopropyl benzene.

In a third aspect, the present invention is directed to a medical devicecomprising: a catheter shaft; and an expandable balloon carried by thecatheter shaft; wherein the balloon comprises an irradiationcross-linked mixture of a polyamide elastomer and no more than about 1.5percent by weight of at least one additional cross-linking reactant, thecross-linking reactant comprising triallyl cyanurate or triallylisocyanurate. Preferably, the balloon comprises an amount of thecross-linking reactant sufficient to give the balloon a strengthgenerally about equal to and in some cases perhaps greater than that ofa balloon composed of the polyamide elastomer and comparablycross-linked by irradiation, but in the absence of any cross-linkingreactant, agent or promoter.

In this third aspect, the balloon of the medical device preferablycomprises a mixture of the polyamide elastomer and the cross-linkingreactant which has been cross-linked by irradiation by an electron beamor by ultraviolet, or X- or gamma rays. Even more preferably, theballoon comprises a mixture of the polyamide elastomer and thecross-linking reactant which has been cross-linked by exposure to about0.5 to about 20 megarads of radiation. The balloon is preferably formedby inflation of the mixture of the polyamide elastomer and thecross-linking reactant after the mixture has been cross-linked byirradiation.

As in the first aspect of the present invention, the balloon of themedical device of the second and third aspects of the present inventionpreferably comprises a polyester amide, a polyether ester amide or apolyether amide, and more preferably comprises a nylon block copolymerincluding polyether blocks separated by polyamide blocks, such as PEBAX®brand nylon block copolymer.

In a fourth aspect, the present invention is directed to a process forassembling a medical device, the medical device comprising an expandableballoon, and the process comprising: creating a mixture of a polyamideelastomer and at least one additional cross-linking reactant, thecross-linking reactant comprising: (a) a difunctional material selectedfrom the class consisting of diallyl adipate; diallyl carbonate; diallylmaleate; diallyl succinate; diallyl tetrabromophthalate; diethyldiallylmalonate; dimethyl diallylmalonate; and2,2,6,6-tetrabromobisphenol A diallyl ether; (b) a trifunctionalmaterial selected from the class consisting of2,5-diallyl-4,5-dimethyl-2-cyclopenten-1-one; diallyl fumarate; diallylitaconate; 1,3,5-triallyl-2-methoxybenzene; triallyl trimesate (triallyl1,3,5-benzenetricarboxylate); triallyl trimellitate (triallyl1,2,4-benzenetricarboxylate); and pentaerythritol triallyl ether; (c) atetrafunctional material selected from the class consisting oftetraallyl cis,cis,cis,cis-cyclopentane-1,2,3,4-tetracarboxylate; andN,N,N′,N′-tetraallylethylenediamine; or (d) an aromatic moleculecontaining at least two ring substituents, each of the ring substituentshaving labile hydrogens at a benzylic site therein; cross-linking themixture of the polyamide elastomer and the at least one additionalreactant by exposing the mixture to a suitable fluence of radiation; andforming the cross-linked mixture into the balloon. In a fifth aspect ofthe present invention, this process is instead carried out with at leastone additional cross-linking reactant comprising diallyl phthalate ormeta-phenylene dimaleimide.

The process of the present invention for assembling the medical deviceis preferably carried out with an amount of the cross-linking reactantsufficient to give the balloon a strength generally about equal to, andperhaps in some cases greater than, that of a balloon composed of thepolyamide elastomer and comparably cross-linked by irradiation, but inthe absence of any cross-linking reactant, agent or promoter. It is alsopreferred that the process is carried out with an amount of thecross-linking reactant which, when mixed with the polyamide elastomerand processed, causes the mixture from which the balloon is made to lackappreciable gelling during processing prior to irradiation andcross-linking. More preferably, the process is carried out with amixture comprising about 1 to about 2 percent by weight of thedifunctional material; about 0.5 to about 1.5 percent by weight of thetrifunctional material or the aromatic molecule containing at least tworing substituents, each of the ring substituents having labile hydrogensat a benzylic site therein; or about 0.01 to about 1 percent by weightof the tetrafunctional material. Alternatively, the process can becarried out with about 1 to about 2 percent by weight diallyl phthalateor meta-phenylene dimaleimide.

Cross-linking of the mixture of the polyamide elastomer and the at leastone additional reactant preferably comprises irradiating the mixturewith an electron beam or with ultraviolet, X- or gamma rays. Irradiationis more preferably carried out at a total fluence of about 0.5 to about20 megarads.

The process of the present invention is preferably carried out with thepolyamide elastomers described above. More preferably, the process ofthe present invention is carried out with a nylon block copolymer whichincludes polyether blocks separated by polyamide blocks, such asPEBAXOR® brand nylon block copolymer. When the process is carried outwith an aromatic molecule containing at least two ring substituents,each of the ring substituents having labile hydrogens at a benzylic sitetherein, it is preferred that the molecule is selected from the classconsisting of 1,3,5 triethyl benzene; 1,2,4 triethyl benzene; and 1,3,5triisopropyl benzene. Without regard to the specific polyamide elastomerand the at least one additional reactant employed in the presentinvention, however, it is preferred that the mixing of them is carriedout by compounding (including such steps as melting, mixing andextruding, for example) or by blending.

The process of the present invention for making a medical devicepreferably further comprises forming the mixture of the polyamideelastomer and the at least one additional reactant into tubing, fromwhich the balloon is formed. It is further preferred that the tubing isformed by extruding the mixture of the polyamide elastomer and the atleast one additional reactant. Most preferably, the mixture of thepolyamide elastomer and the at least one additional reactant is thenformed into the balloon by inflation of the tubing. The process of thepresent invention can further comprise connecting the balloon so formedto a catheter shaft, for example, by adhesion or thermal bonding.

In a sixth aspect, the present invention is directed to a process forassembling a medical device, the medical device comprising an expandableballoon, and the process comprising: creating a mixture of a nylon blockcopolymer and no more than about 1.5 percent by weight of at least oneadditional cross-linking reactant, the cross-linking reactant comprisingtriallyl cyanurate or triallyl isocyanurate; cross-linking the mixtureof the polyamide elastomer and the at least one additional reactant byexposing the mixture to a suitable fluence of radiation; and forming thecross-linked mixture into the balloon.

Other than the use of these two specific cross-linking reactants at thespecified amounts, the preferred details of carrying out the process ofthis sixth aspect of the present invention are very comparable to thedetails of carrying out the process of the fourth aspect of theinvention. Most notably, cross-linking of the mixture of the polyamideelastomer and the at least one additional reactant preferably comprisesirradiating the mixture with an electron beam or with ultraviolet, X- orgamma rays. Irradiation is more preferably carried out at a totalfluence of about 0.5 to about 20 megarads. The balloon is preferablyformed by inflation of a tubing extruded from the mixture of thepolyamide elastomer and the at least one cross-linking reactant, thetubing being irradiated before the balloon is formed from it. Theprocess of the sixth aspect of the present invention is most preferablycarried out with a nylon block copolymer including polyether blocksseparated by polyamide blocks, such as PEBAX® brand nylon blockcopolymer.

In a seventh aspect, the present invention is directed to a medicaldevice comprising: a catheter shaft; and an expandable balloon carriedby the catheter shaft; wherein the balloon comprises an irradiationcross-linked mixture of a polyamide elastomer and at least oneadditional cross-linking reactant. This aspect of the invention mayinstead be considered as an improvement in a medical device comprising acatheter shaft and an expandable balloon carried by the catheter shaft,characterized in that the balloon comprises an irradiation cross-linkedmixture of a polyamide elastomer and at least one additionalcross-linking reactant.

As indicated above, the medical device of the present inventionpossesses significant advantages over prior devices for dilating anarrowing or obstruction in a vessel or lumen in a patient, and fordeploying a stent across the site of such a narrowing or obstruction toprevent its restenosis. The balloon of the device of the presentinvention has a generally improved combination of strength (for example,greater tensile strength, burst pressure and/or puncture resistance) andcompliance (the ratio of balloon diameter growth to balloon pressure).Gelling during its manufacture, if present, is limited to an acceptablelevel. The balloon of the device of the present invention is made frommaterials which meet a variety of desirable processing criteria,including thermal stability, non-toxicity, non-volatility, high boilingpoint (preferably, solid at room temperature), high flash point,insensitivity to moisture and commercial availability. A secondpolyamide elastomer or another polyamide (such as nylon) may be added ina minor amount (less than 50 percent by weight or mole fraction), but isnot required.

The principle disclosed above, irradiation cross-linking a polymericmaterial (such as a polyamide elastomer) in the presence of at least oneadditional cross-linking reactant, has other practical uses and can meetthe other problems mentioned above, problems not specifically addressedby the balloon catheter of the aspects disclosed above. Moreparticularly, while a variety of medical devices are presently known inwhich two or more pieces having different chemical or mechanicalproperties are attached or affixed to one another, each piece havingproperties suited to the performance of a desired function, theprinciple of the present invention permits a single piece in a medicaldevice to possess different functional properties at different locationson it. This result is achieved by altering the durometer of the singlepiece at one or more locations via selective cross-linking of the singlepiece at that location or those locations. “Durometer” is again broadlydefined as above, and includes stiffness and resistance to lateraldeformation, as well as related functional properties such as durometerhardness, modulus of elasticity and flexural modulus. The presentinvention thereby avoids the problems associated with medical deviceshaving different pieces of different durometer, such as beingsusceptible to kinking where the different pieces join, and thedifficulty of joining different pieces of small diameter (especiallybelow about 1 mm outside diameter).

In a first additional aspect, the present invention is directed to amedical device comprising a unitarily and continuously formed portionhaving a varying durometer. “Unitarily and continuously” means more thanmerely securing pieces of different durometer to one another. Instead,the unitary, continuous material employed in the present invention is asingle piece, even though the chemical composition or structure of thematerial may be somewhat modified along the length of the piece (due toselective cross-linking). This stands in direct contrast to priordevices in which discrete parts having different durometers are securedto one another. “Durometer” is used in the broad sense identified above.“Varying” means that the unitarily and continuously formed portionpossesses different durometers at at least two different locations ofthe portion. Such different durometers can arise from the presence ofcross-linking at one location and the absence of cross-linking at theother location, or from the presence of different degrees ofcross-linking at the two different locations. The latter can be broughtabout by exposing the two different locations to different totalfluences of cross-linking irradiation.

The unitarily and continuously formed portion of the medical device ofthe present invention can comprise a tubular portion and an inflatableballoon. The inflatable balloon is preferably a separate piece connectedto the tubular portion, although the inflatable balloon can be unitarilyand continuously formed with the tubular portion. In the former case,the tubular portion itself has a varying durometer, while in the lattercase, the inflatable balloon and the tubular portion have differentdurometers. Instead of a balloon, the medical device can comprise ananchor structure unitarily and continuously formed with the tubularportion, the anchor structure and the tubular portion having differentdurometers. The anchor structure can comprise a malecot, a pigtail, aloop or a comparable structure for maintaining the position of themedical device in the patient.

The tubular portion can comprise a catheter shaft, for example, acatheter shaft having at least first and second catheter shaft segmentsof different durometer, the first and second catheter shaft segmentsbeing unitarily and continuously formed. Preferably, one of the at leastfirst and second catheter shaft segments comprises a catheter tip whilethe other of the catheter shaft segments comprises a catheter body. Ingeneral, the catheter body preferably has a greater durometer than thecatheter tip, although there may be alternative situations in which itis preferred that the catheter tip has a greater durometer than thecatheter body.

The catheter tip can be the anchor structure mentioned above or can bean inflatable balloon. The medical device of the present invention isconfigured as a needle set, however, and in such a case the catheter tippreferably includes a distal end and a step or ledge formed in thecatheter tip near the distal end. “Step” and “ledge” can be consideredsynonymous for the purposes of the present invention, as they eachperform the same function in the present invention. The medical deviceof the present invention then further comprises a needle receivable inthe catheter shaft, the needle bearing on it a ring, collar orenlargement engageable with or abuttable against the step or ledge inthe catheter tip. “Ring,” “collar” and “enlargement” can similarly beconsidered synonymous for the purposes of the present invention, sincethey each perform the same function in the present invention.

In yet a further alternative embodiment, the unitarily and continuouslyformed portion of the medical device of the present invention cancomprise at least first and second unitarily and continuously formedparts having different durometers, and a transition zone of continuouslyvarying durometer connecting the first and second parts, the transitionzone being unitarily and continuously formed with the first and secondparts. The first or second part of the unitarily and continuously formedportion can be the catheter tip or anchor structure disclosed above, aproximal or distal catheter segment or the inflatable balloon disclosedbelow. The transition zone can of course be absent, that is, it mayextend only so far as may result from diffraction of the cross-linkingirradiation at the edge of a shield which protects one of the first orsecond parts from irradiation. Alternatively, the unitarily andcontinuously formed portion can extend longitudinally, and the durometerof the portion can vary continuously along the entire length of theportion.

The medical device of the present invention is useful in forminginfusion, drainage, diagnostic, therapeutic or balloon catheters, andmore advantageously, in forming microcatheters having an outsidediameter less than about 1 mm. Relating specifically to ballooncatheters, for example, the medical device of the present invention cancomprise a catheter shaft having an outer catheter shaft and an innercatheter shaft received in the outer catheter shaft, the outer cathetershaft comprising the unitarily and continuously formed portion disclosedabove. Preferably, an inflatable balloon can be connected to the outerand inner catheter shafts. The outer catheter shaft can instead comprisean inflatable balloon unitarily and continuously formed with theunitarily and continuously formed portion, the inflatable balloon andthe unitarily and continuously formed portion having differentdurometers. In either case, the inflatable balloon has a distal endsealed against the inner catheter shaft so that the space between theinner and outer catheter shafts serves as a lumen for the introductionand removal of pressurized fluid for inflation and deflation of theballoon.

The unitarily and continuously formed portion of the medical device ofthe present invention preferably generally comprises any of the balloonmaterials described herein. Thus, the unitarily and continuously formedportion preferably comprises an irradiation cross-linkable mixture of apolyamide elastomer and at least one additional cross-linking reactant.It should be noted that it is appropriate in these additional aspects ofthe invention to describe the material as “cross-linkable” rather than“cross-linked,” because one part or another of the unitarily andcontinuously formed portion may not be cross-linked at all.

The at least one additional cross-linking reactant can comprise: (a) adifunctional material selected from the class consisting of diallyladipate; diallyl carbonate; diallyl maleate; diallyl succinate; diallyltetrabromophthalate; diethyl diallylmalonate; dimethyl diallylmalonate;and 2,2,6,6-tetrabromobisphenol A diallyl ether; (b) a trifunctionalmaterial selected from the class consisting of2,5-diallyl-4,5-dimethyl-2-cyclopenten-1-one; diallyl fumarate; diallylitaconate; 1,3,5-triallyl-2-methoxybenzene; triallyl trimesate (triallyl1,3,5-benzenetricarboxylate); triallyl trimellitate (triallyl1,2,4-benzenetricarboxylate); and pentaerythritol triallyl ether; (c) atetrafunctional material selected from the class consisting oftetraallyl cis,cis,cis,cis-cyclopentane-1,2,3,4-tetracarboxylate; andN,N,N′,N′-tetraallylethylenediamine; or (d) an aromatic moleculecontaining at least two ring substituents, each of the ring substituentshaving labile hydrogens at a benzylic site therein; the unitarily andcontinuously formed portion then comprising at least first and secondparts unitarily and continuously formed with one another, at least oneof the first and second parts being exposed to cross-linkingirradiation. Preferably, the mixture comprises about 1 to about 3percent by weight of the difunctional material; about 0.5 to about 1.5percent by weight of the trifunctional material or the aromatic moleculecontaining at least two ring substituents, each of the ring substituentshaving labile hydrogens at a benzylic site therein; or about 0.01 toabout 1 percent by weight of the tetrafunctional material.

Without regard to the specific polyamide elastomer or additionalcross-linking reactant employed, the unitarily and continuously formedportion can comprise at least first and second parts unitarily andcontinuously formed with one another, at least one of the first andsecond parts being exposed to cross-linking irradiation, or the firstand second parts being exposed to different amounts of cross-linkingirradiation. Preferably, the unitarily and continuously formed portioncomprises an amount of the at least one cross-linking reactantsufficient to give the unitarily and continuously formed portion astrength generally about equal to that of a unitarily and continuouslyformed portion composed of the polyamide elastomer and comparablycross-linked by irradiation, but in the absence of any cross-linkingreactant, agent or promoter.

Cross-linking of the unitarily and continuously formed portion, in partor in whole, is brought about in any convenient or conventional manner,for example, by irradiation with an electron beam or with ultraviolet,X- or gamma rays. “In part” refers not to cross linking which is broughtabout at least in part by the indicated forms of irradiation, but rathermeans merely that at least part of the mixture making up the portion(even if not all of it) has been irradiation cross-linked. Preferably,the unitarily and continuously formed portion comprises a mixture of thepolyamide elastomer and the at least one cross-linking reactant whichhas been cross-linked, at least in part, by exposure to about 0.5 toabout 60 megarads of radiation, preferably about 30 megarads. It shouldbe noted that degradation of some of the mixtures disclosed herein maybegin to occur at the 55 to 60 megarad level.

As an aside, it should be noted that it is preferred that the amount ofthe at least one additional cross-linking reactant be uniform throughoutthe mixture making up the unitarily and continuously formed portion ofthe medical device. Varying the degree of cross-linking is thenconveniently achieved by varying the fluence of irradiation to which theparts of the portion are exposed. It is certainly possible, however,that there might be circumstances under which it would be desirable touse a non-uniform mixture, and such use is contemplated as fallingwithin the scope of the present invention.

The mixture from which the unitarily and continuously formed portion ofthe medical device of the present invention is fabricated canalternatively preferably comprise an irradiation cross-linkable mixtureof a polyamide elastomer and an aromatic molecule containing at leasttwo ring substituents, each of the ring substituents having labilehydrogens at a benzylic site therein, selected from the class consistingof 1,3,5 triethyl benzene; 1,2,4 triethyl benzene; and 1,3,5triisopropyl benzene. The mixture preferably comprises at least onepolyamide elastomer selected from the class consisting of polyesteramides, polyether ester amides and polyether amides, and more preferablycomprises a nylon block copolymer. Even more preferably, the mixturecomprises a nylon block copolymer including polyether blocks separatedby polyamide blocks.

As a further alternative, the unitarily and continuously formed portionof the medical device of the present invention preferably comprises anirradiation cross-linkable mixture of a polyamide elastomer and about0.25 to about 5 percent by weight of triallyl cyanurate or triallylisocyanurate as the at least one additional cross-linking reactant. Yetfurther, the at least one cross-linking reactant can instead preferablycomprise diallyl phthalate or meta-phenylene dimaleimide, morepreferably at about 1 to about 2 percent by weight in the mixture.

The most preferable mixture for use in the medical device of the presentinvention may be a mixture of a nylon block copolymer includingpolyether blocks separated by polyamide blocks, and about 3 percent byweight triallyl isocyanurate. Such a mixture preferably also includes upto about 25 percent by weight of a nylon, more preferably about 10percent by weight nylon.

Without regard to its particular composition, however, the unitarily andcontinuously formed portion of the medical device of the presentinvention can comprise a tubular portion and an inflatable balloonunitarily and continuously formed with the tubular portion, theinflatable balloon being formed by inflation of the mixture of thepolyamide elastomer and the at least one cross-linking reactant after atleast part of the mixture has been cross-linked by irradiation.

In a second additional aspect, the present invention is directed to amedical device comprising a unitarily and continuously formed portionhaving a varying durometer, and a catheter shaft having an outercatheter shaft and an inner catheter shaft received in the outercatheter shaft, the outer catheter shaft comprising the unitarily andcontinuously formed portion; wherein the outer catheter shaft furthercomprises an inflatable balloon unitarily and continuously formed withthe unitarily and continuously formed portion, the inflatable balloonand the unitarily and continuously formed portion having differentdurometers; and wherein the unitarily and continuously formed portioncomprises an irradiation cross-linkable mixture of a nylon blockcopolymer including polyether blocks separated by polyamide blocks, andabout 3 percent by weight triallyl isocyanurate. This aspect of thepresent invention is particularly useful in forming balloonmicrocatheters, having an outside diameter of less than about 1 mm. Theinflatable balloon can alternatively be a distinct piece separate fromthe catheter shaft, connected to it but not unitarily and continuouslyformed with it.

In a third additional aspect, the present invention is directed to amedical device comprising a unitarily and continuously formed portionhaving a varying durometer, the unitarily and continuously formedportion comprising a catheter shaft having at least first and secondcatheter shaft segments of different durometer, the first and secondcatheter shaft segments being unitarily and continuously formed; whereinone of the at least first and second catheter shaft segments comprises acatheter tip and the other of the at least first and second cathetershaft segments comprises a catheter body, the catheter body having agreater durometer than the catheter tip; and wherein the unitarily andcontinuously formed portion comprises an irradiation cross-linkablemixture of a nylon block copolymer including polyether blocks separatedby polyamide blocks, and about 3 percent by weight triallylisocyanurate. The catheter tip may of course be the anchor structure orpart of a needle set.

In a fourth additional aspect, the present invention is directed to aprocess for assembling a medical device, the medical device comprising aunitarily and continuously formed portion having a varying durometer,and the process comprising: creating an irradiation cross-linkablemixture of a polyamide elastomer and at least one additionalcross-linking reactant; forming the mixture into a unitarily andcontinuously formed portion; and exposing the unitarily and continuouslyformed portion, at least in part, to cross-linking irradiation. Themixture is preferably formed into a tubular portion suited to any of avariety of purposes.

The step of forming the unitarily and continuously formed portion can,for example, comprise forming a portion intended for use as aninflatable balloon unitarily and continuously with the tubular portion,wherein the exposing step comprises exposing at least one of the tubularportion and the portion intended for use as an inflatable balloon, tocross-linking irradiation. The process of the present invention thenpreferably additionally comprises heating and applying pressure to theportion intended for use as an inflatable balloon so as to form asuitable inflatable balloon from that portion. The preferred processingconditions are the same as disclosed with respect to prior aspects ofthe invention, and as described in detail below. The resulting tubularportion and unitarily and continuously formed inflatable balloon havedifferent durometers. The inflatable balloon can alternatively be adistinct piece separate from the catheter shaft, connected to it but notunitarily and continuously formed with it.

Alternatively, the step of forming the unitarily and continuously formedportion can instead preferably comprise forming an anchor structureunitarily and continuously with the tubular portion, wherein theexposing step comprises exposing at least one of the anchor structureand the tubular portion to cross-linking irradiation. The step offorming an anchor structure can comprise forming a malecot, a pigtail, aloop or the like. As above, the resulting tubular portion and unitarilyand continuously formed anchor structure have different durometers,improving anchoring of the tubular portion in the patient.

As a further alternative, the step of forming the unitarily andcontinuously formed portion can comprise forming a catheter shaft fromthe mixture, the catheter shaft preferably having at least first andsecond unitarily and continuously formed catheter shaft segments. Theexposing step then preferably comprises exposing at least one of thefirst and second catheter shaft segments to cross-linking irradiation,to give them different durometers. The exposing step can compriseexposing only one of the first and second catheter shaft segments toirradiation, or can comprise exposing the first and second cathetershaft segments to different amounts of cross-linking irradiation.

The step of forming a catheter shaft can preferably further compriseforming one of the first and second catheter shaft segments into acatheter tip and the other of the first and second catheter segmentsinto a catheter body. Either or both of the catheter body and thecatheter tip can then be exposed to cross-linking irradiation, givingthem different durometers. Prior to such exposure, however, the cathetertip can be formed so as to give it desired characteristics. For example,the step of forming a catheter shaft can further comprise forming a stepor ledge in the catheter tip near a distal end of the catheter tip, andthe process further comprise introducing a needle into the cathetershaft, the needle bearing on it a ring, collar or enlargement engageablewith or abuttable against the step or ledge in the catheter tip. As withneedle sets having a discrete catheter tip of harder material, theneedle set resulting from the process of the present invention is lesssubject to sliding of the catheter body with respect to the needleduring introduction into a patient (“accordioning”), while avoiding thedrawbacks associated with attempting to affix a discrete catheter tip tothe catheter body.

The change of durometer between first and second unitarily andcontinuously formed parts of the unitarily and continuously formedportion can be sharp, achieved simply by placing a shield of uniformthickness between the unitary and continuously formed portion and asource of cross-linking irradiation, prior to the exposing step. It ispreferred, however, that the exposing step instead comprises exposing aunitarily and continuously formed transition zone between the first andsecond parts to a continuously varying amount of cross-linkingirradiation. This can be achieved, for example by placing a shield ofvarying density between the unitarily and continuously formed portionand a source of cross-linking irradiation, prior to the exposing step.The shield can have a taper which attenuates the exposure to irradiation(and thereby attenuates cross-linking) in the transition zone covered bythe taper. A continuous change over part or all of the longitudinalextent of the unitarily and continuously formed portion can be achievedwith a similar shield.

This aspect of the invention can also be employed to form a ballooncatheter, and in particular, a balloon microcatheter having an outerdiameter of about 1 mm or less. In such a process, the forming stepcomprises forming a catheter shaft comprising an outer catheter shaftand an inner catheter shaft received in the outer catheter shaft, theouter catheter shaft comprising the irradiation cross-linkable mixture.The forming step further preferably comprises unitarily and continuouslyforming with the outer catheter shaft a portion intended for use as aninflatable balloon, wherein the exposing step is carried out so as toprovide different durometers to the outer catheter shaft and the portionintended for use as an inflatable balloon by exposing at least one ofthe outer catheter shaft and the portion intended for use as aninflatable balloon to cross-linking irradiation. The process furtherpreferably comprises heating and applying pressure to the portionintended for use as an inflatable balloon so as to form an inflatableballoon from that portion. The inner catheter shaft is then insertedinto the outer catheter shaft and through the balloon portion, and thedistal end of the balloon secured to and fluidly sealed in aconventional fashion to the inner catheter shaft. A space between theouter and inner catheter shafts defines the lumen for the introductionand removal of pressurized inflation fluid to the inflatable balloon.Alternatively, however, the inflatable balloon can be a separate piececonnected to the outer and inner catheter shafts, unitarily andcontinuously formed with neither of them.

Expressed in its most general terms, in the process of the presentinvention, the forming step is preferably carried out so as to yield aunitarily and continuously formed portion comprising at least first andsecond parts unitarily and continuously formed with one another, whereinthe exposing step comprises exposing at least one of the first andsecond parts to cross-linking irradiation. The different parts of theunitarily and continuously formed portion are thereby given differentdurometers. This is most easily achieved by exposing only one of thefirst and second parts of the unitarily and continuously formed portionto cross-linking irradiation. It may be desirable, however, that theexposing step comprise exposing the first and second unitarily andcontinuously formed parts to different amounts of cross-linkingirradiation.

The process of the present invention is preferably carried out employingany of the cross-linkable mixtures disclosed herein. Accordingly, theprocess of the present invention can be carried out with a cross-linkingreactant comprising: (a) a difunctional material selected from the classconsisting of diallyl adipate; diallyl carbonate; diallyl maleate;diallyl succinate; diallyl tetrabromophthalate; diethyl diallylmalonate;dimethyl diallylmalonate; and 2,2,6,6-tetrabromobisphenol A diallylether; (b) a trifunctional material selected from the class consistingof 2,5-diallyl-4,5-dimethyl-2-cyclopenten-1-one; diallyl fumarate;diallyl itaconate; 1,3,5-triallyl-2-methoxybenzene; triallyl trimesate(triallyl 1,3,5-benzenetricarboxylate); triallyl trimellitate (triallyl1,2,4-benzenetricarboxylate); and pentaerythritol triallyl ether; (c) atetrafunctional material selected from the class consisting oftetraallyl cis,cis,cis,cis-cyclopentane-1,2,3,4-tetracarboxylate; andN,N,N′,N′-tetraallylethylenediamine; or (d) an aromatic moleculecontaining at least two ring substituents, each of the ring substituentshaving labile hydrogens at a benzylic site therein. In such a case, theprocess is preferably carried out with a mixture comprising about 1 toabout 2 percent by weight of the difunctional material; about 0.5 toabout 1.5 percent by weight of the trifunctional material or thearomatic molecule containing at least two ring substituents, each of thering substituents having labile hydrogens at a benzylic site therein; orabout 0.01 to about 1 percent by weight of the tetrafunctional material.

The process of the present invention is preferably carried out with anamount of the at least one cross-linking reactant sufficient to give theunitarily and continuously formed portion a strength generally aboutequal to that of a unitarily and continuously formed portion composed ofthe nylon block copolymer and comparably cross-linked by irradiation,but in the absence of any cross-linking reactant, agent or promoter. Theexposing step of the present invention preferably comprises irradiatingthe mixture with an electron beam or with ultraviolet, X- or gamma rays,at a total fluence of about 0.5 to about 60 megarads, preferably about30 megarads.

The mixing of the polyamide elastomer and the at least one additionalreactant can be conveniently carried out by compounding, while thetubular portion can be formed by extruding the mixture of the polyamideelastomer and the at least one additional reactant.

The process of the present invention is preferably carried out with atleast one polyamide elastomer selected from the class consisting ofpolyester amides, polyether ester amides and polyether amides. Theprocess is more preferably carried out with a polyamide elastomercomprising a nylon block copolymer, most preferably with a nylon blockcopolymer including polyether blocks separated by polyamide blocks. Itis probably most preferable that the process be carried out with about 3percent by weight triallyl isocyanurate as the additional cross-linkingreactant in a mixture which also includes about 10 percent by weightnylon.

The process of the present invention can instead be carried out with anirradiation cross-linkable mixture of a polyamide elastomer and anaromatic molecule containing at least two ring substituents, each of thering substituents having labile hydrogens at a benzylic site therein,selected from the class consisting of 1,3,5 triethyl benzene; 1,2,4triethyl benzene; and 1,3,5 triisopropyl benzene.

It is alternatively preferred that the process of the present inventionbe carried out with a mixture of a polyamide elastomer and no more thanabout 5 percent by weight of at least one additional cross-linkingreactant, the cross-linking reactant comprising triallyl cyanurate ortriallyl isocyanurate. The process can also be carried out with amixture comprising about 1 to about 2 percent by weight of across-linking reactant comprising diallyl phthalate or meta-phenylenedimaleimide.

In a fifth and final additional aspect, the present invention isdirected to a process for assembling a medical device, the medicaldevice comprising a unitarily and continuously formed portion having avarying durometer, and the process comprising: creating an irradiationcross-linkable mixture of a polyamide elastomer and at least oneadditional cross-linking reactant; forming the mixture into a unitarilyand continuously formed portion; and exposing the unitarily andcontinuously formed portion, at least in part, to cross-linkingirradiation; wherein the step of forming the portion comprises formingthe mixture into a tubular portion; wherein the forming step is carriedout so as to yield a unitarily and continuously formed portioncomprising at least first and second parts unitarily and continuouslyformed with one another, and the exposing step comprises exposing atleast one of the first and second parts to cross-linking irradiation;wherein the exposing step comprises irradiating the mixture with anelectron beam at a total fluence of about 0.5 to about 60 megarads;wherein the mixing of the polyamide elastomer and the at least oneadditional reactant is carried out by compounding, and wherein thetubular portion is formed by extruding the mixture of the polyamideelastomer and the at least one additional reactant; and wherein theprocess is carried out with a mixture comprising: a nylon blockcopolymer including polyether blocks separated by polyamide blocks,about 3 percent by weight triallyl isocyanurate and about 10 percent byweight nylon.

BRIEF DESCRIPTION OF THE DRAWINGS

A better understanding of the present invention will now be had uponreference to the following detailed description, when read inconjunction with the accompanying drawing, wherein like referencecharacters refer to like parts throughout the several views, and inwhich:

FIG. 1 is a partial cross-sectional view of the medical device of thepreferred embodiment of the present invention;

FIG. 2 is a partial cross-sectional view of a step in the process forassembling the medical device of the preferred embodiment of the presentinvention;

FIG. 3 is a flow chart of the process of assembling the medical deviceof the preferred embodiment of the present invention;

FIG. 4 is a side view of the medical device of another preferredembodiment of the present invention, and of apparatus for itsmanufacture;

FIG. 5 is a partial cross-sectional view of a portion of anotherpreferred embodiment of the present invention;

FIG. 6 is a side view of a portion of another preferred embodiment ofthe present invention;

FIG. 7 is a side view of a portion of another preferred embodiment ofthe present invention;

FIG. 8 is a side view of a portion of another preferred embodiment ofthe present invention; and

FIG. 9 is a cross-sectional view of another preferred embodiment of thepresent invention.

DETAILED DESCRIPTION OF THE INVENTION

With reference first to FIG. 1, an embodiment of a medical device 10according to the present invention is thereshown, useful for dilating anarrowing or obstruction in a vessel or lumen in a patient, and/or fordeploying a stent (not shown in the Figures) across the site of such anarrowing or obstruction to prevent its restenosis. The medical device10 of the present invention first comprises a catheter shaft 11. Thecatheter shaft 11 is preferably a multi-element shaft, and preferablycomprises an inner catheter shaft 12 received in and extendinglongitudinally through a lumen 20 in an outer catheter shaft 14. Thecatheter shaft 11 could alternatively comprise a single catheter shaft(not shown) having at least one lumen formed longitudinally therein. Theinner and outer catheter shafts 12 and 14 preferably comprise medicalgrade polyethylene, polyamide or other suitable medical grade materials,and are of a diameter or French size suited to the particular procedurein which it is intended to use the device 10. The inner and outercatheter shafts 12 and 14 can comprise the same or different suchmaterials.

The device 10 of the present invention also comprises an inflatableballoon 18 carried on the catheter shaft 11. The balloon 18 comprises anirradiation cross-linked mixture of a polyamide elastomer and at leastone additional cross-linking reactant, the nature of the mixture and itscross-linking being described in more detail below. The balloon 18 isdimensioned and adapted for the particular procedure in which it is tobe employed. Balloon length and inflation diameters suited to variousprocedures are well known, and for brevity need not be recited here.

The balloon 18 is preferably formed separately from the catheter shaft11, and separately from the inner and outer catheter shafts 12 and 14.The balloon 18 is more preferably affixed at its proximal end 17 to thedistal end 15 of the outer catheter shaft 14, and at its distal end 19to the distal end 16 of the inner catheter shaft 12. Affixing can occurby use of a suitable medical grade adhesive 38, or by thermal bonding.

The lumen 20 defined in the outer shaft 14 permits the supply of aninflation fluid from a supply (not shown) and to the interior 24 of theballoon 18. More particularly, the catheter shaft 14 has a lumen endport 22 defined at its distal end 15, placing the balloon interior 24,the catheter shaft lumen 20 and the inflation fluid supply in fluidcommunication with one another. The balloon 18 may carry on it a stentof conventional design (not shown), expanded or permitted to expand uponinflation of the balloon 18.

Either or both of the inner and outer catheter shafts 12 and 14 caninclude one or more other lumens for any of a variety of conventionalpurposes. For example, the inner catheter shaft 12 can include a lumen13 defined longitudinally therein for the introduction or passage of aconventional wire guide therethrough. In use of the medical device 10 ofthe present invention, this wire guide would first be advanced acrossthe narrowing or obstruction to be treated, and the balloon 18 of themedical device 10 then advanced along this wire guide until the balloon18 was positioned across the narrowing or obstruction. Inflation of theballoon 18 then widens the narrowing or obstruction. If the medicaldevice 10 has been supplied with a stent, such inflation deploys thestent at the site of the narrowing or obstruction, preventing restenosisof the site. Of course, any additional lumens in the inner and outercatheter shafts 12 and 14 can be employed for other conventionalpurposes, such as fluid drainage or injection, or the passage of anothercatheter or other medical device or instrument.

As indicated above, the balloon 18 comprises an irradiation cross-linkedmixture of a polyamide elastomer and at least one additionalcross-linking reactant which acts to covalently link the chains of thepolyamide elastomer. The polyamide elastomer can be a polyester amide, apolyether ester amide or a polyether amide. Specific commercial examplesof such materials include ESTAMID®, PEBAX®, VESTAMID®, GRILAMID® andGRILON® brand polymers. The polyamide elastomer used to make the balloon18 is preferably a nylon block copolymer. Nylon block copolymersexpected to be useful in making the balloon 18 of the medical device 10of the present invention include polyamide blocks separated by polyetherblocks or other elastomeric blocks or segments, such as polyesters,hydrocarbons or polysiloxanes. Preferably, the polyamide elastomer is anpolyester amide, a polyether ester amide or a polyether amide asdescribed above. More preferably, the nylon block copolymer employed inthe mixture from which the balloon 18 is formed comprises a nylon blockcopolymer including polyamide blocks separated by polyether blocks. Mostpreferably, the nylon block copolymer is PEBAX® brand nylon blockcopolymer. Although probably not preferred, the mixture from which theballoon 18 of the medical device 10 of the present invention can alsocomprise a minor proportion (less than 50 percent by weight or molefraction) of a second polyamide elastomer or another polyamide (such asnylon) similarly capable of being cross-linked by the at least oneadditional cross-linking reactant.

The at least one additional cross-linking reactant can comprise any of avariety of materials. For example, the at least one additionalcross-linking reactant can comprise a difunctional material selectedfrom the class consisting of diallyl adipate; diallyl carbonate; diallylmaleate; diallyl succinate; diallyl tetrabromophthalate; diethyldiallylmalonate; dimethyl diallylmalonate; and2,2,6,6-tetrabromobisphenol A diallyl ether. The mixture from which theballoon 18 is formed preferably comprises about 1 to about 2 percent byweight of such a difunctional material. Alternatively, the at least oneadditional cross-linking material can comprise a trifunctional materialselected from the class consisting of2,5-diallyl-4,5-dimethyl-2-cyclopenten-1-one; diallyl fumarate; diallylitaconate; 1,3,5-triallyl-2-methoxybenzene; triallyl trimesate (triallyl1,3,5-benzenetricarboxylate); triallyl trimellitate (triallyl1,2,4-benzenetricarboxylate); and pentaerythritol triallyl ether. Themixture from which the balloon 18 is formed then preferably comprisesabout 0.5 to about 1.5 percent by weight of such a trifunctionalmaterial. The amount of tri-functional material required for the balloon18 will likely be somewhat less than the amount of difunctional materialrequired, because the additional functional group of the trifunctionalmaterial provides an additional site for the material to bond to thechains of the polyamide elastomer.

The at least one additional cross-linking reactant can alternativelycomprise a tetrafunctional material selected from the class consistingof tetraallyl cis,cis,cis,cis-cyclopentane-1,2,3,4-tetracarboxylate; andN,N,N′,N′-tetraallylethylenediamine. The mixture from which the balloon18 is formed then preferably comprises about 0.01 to about 1 percent byweight of the tetrafunctional material. The dramatically lower value ispossible because the fourth functional group may permit cross-linking tobe achieved even more readily than with trifunctional materials;however, depending upon the sterics of the particular polyamideelastomer and the particular tetrafunctional material selected, such lowvalues may not actually be enjoyed. The at least one additionalcross-linking reactant can instead comprise an aromatic moleculecontaining at least two ring substituents, each of the ring substituentshaving labile hydrogens at a benzylic site therein.

The mixture from which the balloon 18 is formed then preferablycomprises about 0.5 to about 1.5 percent by weight of the aromaticmolecule containing at least two ring substituents, each of the ringsubstituents having labile hydrogens at a benzylic site therein. Thearomatic molecule containing at least two ring substituents, each of thering substituents having labile hydrogens at a benzylic site therein, ispreferably selected from the class consisting of 1,3,5 triethyl benzene;1,2,4 triethyl benzene; and 1,3,5 triisopropyl benzene. As indicatedabove, the aromatic molecule containing at least two ring substituents,each of the ring substituents having labile hydrogens at a benzylic sitetherein, may instead be any of a wide variety of suitably-substitutedaromatic molecules; these three are preferred because they arecommercially available at the present time. Finally, the at least oneadditional cross-linking reactant can comprise no more than about 1.5percent by weight of triallyl cyanurate or triallyl isocyanurate, orabout 1 to about 2 percent by weight of diallyl phthalate ormeta-phenylene dimaleimide.

Without regard to the particular at least one additional cross-linkingreactant employed, the mixture from which the balloon 18 is formedcomprises an amount of the at least one additional cross-linkingreactant sufficient to give the balloon 18 a strength generally aboutequal to, and in some cases perhaps greater than, that of a ballooncomposed of the polyamide elastomer and comparably cross-linked byirradiation, but in the absence of any cross-linking reactant, agent orpromoter.

The mixture is preferably irradiated before the balloon 18 is formed byinflation as described below, or otherwise formed. The mixture of thepolyamide elastomer and the at least one additional cross-linkingreactant can be cross-linked by irradiation with an electron beam orwith ultraviolet, X- or gamma rays, preferably with an electron beamsince it may be more efficient and may achieve satisfactorycross-linking at lower fluences than the others. Preferably, the mixtureis cross-linked by exposure to a total fluence of about 0.5 to about 20megarads.

The general process for forming a balloon 18 from the mixture of thepolyamide elastomer and the at least one additional cross-linkingreactant, and incorporating such a balloon into a medical device 10, cannow be readily understood. A familiarity with the principles ofmanufacturing balloons for medical devices and the associated regulatoryrequirements is presumed. Those skilled in the art of manufacturingballoons for medical devices should readily be able to adapt the generalprocess described herein to the particular materials being employed.

In its simplest form, the process for assembling a medical device 10comprising an expandable balloon 18 comprises the steps of creating amixture of a polyamide elastomer and at least one additionalcross-linking reactant as described above; cross-linking the mixture ofthe polyamide elastomer and the at least one additional cross-linkingreactant by exposing the mixture to a suitable fluence of radiation; andforming the resulting cross-linked mixture into the balloon 18. Thedetails of the preferred composition of the nylon block copolymer andthe at least one additional cross-linking reactant, as well as thepreferred types and fluences of irradiation, are recited above; forbrevity, these will not be repeated.

The process of the present invention can be carried out with any of avariety of specific process steps known to be useful for assemblingballoon-type medical devices from materials other than the specificmixtures of polyamide elastomers and cross-linking reactants disclosedherein. Accordingly, the description of any particular steps or anyspecific apparatus for performing any particular steps should not betaken as limiting the scope of the broad process disclosed herein. Forpurposes of illustration, however, a preferred process according to thepresent invention for assembling the medical device 10 is shown in theflow chart of FIG. 3. First, the polyamide elastomer and the at leastone additional cross-linking reactant are intimately mixed together (box42). Such mixing is most conveniently carried out by compounding and/orblending the elastomer and the cross-linking reactant together. Next,the mixture of the polyamide elastomer and the at least one additionalcross-linking reactant are formed into a shape suitable for irradiationand further processing. Conveniently, the mixture of the elastomer andthe cross-linking reactant are extruded into the shape of a tubing 26(box 44). Other extrusion shapes can be employed as needed or desired.The tubing 26 (or other form of the mixture) is then irradiated tocross-link the material (block 46). Irradiation is most convenientlycarried out by exposing the tubing 26 to an electron beam or to a sourceof ultraviolet, X- or gamma rays, the electron beam probably beingpreferred.

The cross-linked material, in the physical form of the tubing 26, isthen formed into the balloon 18 (box 48). The tubing 26 is mostconveniently formed into the balloon 18 by applying heat and aninflation medium or fluid to the tubing 26. A simplified view of anapparatus for performing this balloon-forming step is shown in FIG. 2.The tubing 26 is introduced into a heatable mold 28 having first, secondand third mold parts 32, 34 and 36, whose facing surfaces define betweenthem a mold cavity 30. The mold cavity is shaped and sized substantiallythe same as the ultimately desired shape and size of the balloon 18,shrinkage and other conventional molding concerns having been taken intoaccount. The mold 28 is heated, thereby warming the tubing 26, and asource 40 of pressurized inflation medium is applied to an open end ofthe tubing 26 outside the mold 28. Sufficient inflation pressure issupplied from the source 40 to cause the tubing 26 to expand within themold 28 until the tubing 26 contacts the facing surfaces of the moldparts 32, 34 and 36, and takes on the shape of the mold cavity 30.Pressure in the tubing 26 is then relieved, the tubing 26 deflated andremoved from or allowed to exit the mold 28 for further processing asneeded. Stretching of the tubing 26 and/or repeated heating or inflationof the tubing 26 can be performed in the conventional manner, as neededor as desired to achieve the balloon 18 (as a portion of the tubing 26).

Once the balloon 18 is formed as a part of the tubing 26, the balloon 18is cut from the tubing 26 and connected to the catheter shaft 11 (box50), for example, by affixing the proximal and distal ends 17 and 19 ofthe balloon 18 to the distal ends 16 and 15 of the inner and outercatheter shafts 12 and 14. Affixing can be carried out by use of themedical grade adhesive 38 described above, or by heat bonding.

The process of the present invention forming the medical device 10 is ofcourse not limited to the particular steps described above. A widevariety of steps and methods for forming medical device balloons fromother materials are well-known, and are expected to be useful in theassembly of the medical device 10. For example, molds having other thanthree pieces can be used; indeed, a single balloon for a medical devicecan be formed with no mold at all, just inflation of a parison havingonly an inlet for an inflation fluid, and no outlet.

EXAMPLES

A variety of examples of irradiation cross-linked mixtures of PEBAX®brand nylon block copolymer with differing amounts of triallyl cyanurateor triallyl isocyanurate (“% XL”) as the at least one cross-linkingreactant are disclosed in Tables 1 through 4 annexed hereto. The Frenchsize indicates the size of the tubing 26 from which the balloon 18 ismade, while the Double Wall (in inches) indicates twice the wallthickness of the balloon 18 ultimately formed (the thickness of theopposing balloon walls when pressed together). In the MaterialFormulations column in the Tables, 7233SAO1 and 6333SNO1 refer to twodifferent grades of PEBAX® brand copolymers. Formulations containingboth grades thus constitute mixtures of two different copolymers. Theparticular nylon block copolymer mixtures used in the examples werespecially ordered mixtures, mixtures which it is believed are nototherwise commercially distributed at this time. More specifically, itis believed that Foster Corporation, Dayville, Conn., commerciallydistributes (under the trade name FOSTALINK™) mixtures containing PEBAX®brand copolymer and 2 percent or more by weight of either triallylcyanurate or triallyl isocyanurate. Mixtures containing 0.125 to 1.00percent weight of either triallyl isocyanurate or triallyl isocyanuratewere requested from Foster Corporation, and were used in the examples inthe Tables. As an aside, it should be noted that it is not presentlyknown which of the two materials, the triallyl cyanurate or the triallylisocyanurate, was included in the FOSTALINK™ materials used in theexamples.

A number of comparative examples are shown in the Tables, in which thetriallyl cyanurate or triallyl isocyanurate is not present; in which themixture of the nylon block copolymer and the at least one additionalcross-linking reactant is not irradiated; in which the at least oneadditional cross-linking reactant is omitted; and in which nylon 12 isadded to the nylon block copolymer at an indicated percentage by weight.Irradiation at the indicated fluence occurred by exposure to an electronbeam; as indicated above, other forms of irradiation are expected to beless efficient than electron beam at performing the cross-linkingdesired in the present invention, and higher fluences of ultraviolet, X-or gamma rays may be required to achieve the same results.

Table 1 contains comparative examples of mixtures (MaterialFormulations) employed to form tubing of the indicated French size anddiameters into balloons. Except for the last entry (which comprisedsolely nylon 6/6), the comparative examples of Table 1 were carried outwith mixtures comprising a PEBAX® brand nylon block copolymer and 2 or 3percent by weight of a triallyl cyanurate or triallyl isocyanurate;mixtures comprising a PEBAX® brand nylon block copolymer, 3 percent byweight of a triallyl cyanurate or triallyl isocyanurate and 10 percentby weight of a nylon 12; or mixtures comprising a PEBAX® brand nylonblock copolymer and 10 percent by weight of a nylon 12, without anytriallyl cyanurate or triallyl isocyanurate.

Table 2 contains comparative examples of mixtures comprising a nylon 12with no cross-linking reagent; a PEBAX®) brand nylon block copolymerwith no cross-linking reagent; and a PEBAX® brand nylon block copolymerwith 2 percent by weight of a triallyl cyanurate or triallylisocyanurate, as well as mixtures containing 3 percent by weight of atriallyl cyanurate or triallyl isocyanurate and further including asecond PEBAX® brand nylon block copolymer or a nylon 12.

Table 3 contains further comparative examples of such mixtures.

Finally, Table 4 contains examples of mixtures useful for forming theballoon 18 of the medical device 10 of the present invention. Moreparticularly, the mixtures of the examples shown in Table 4 comprise aPEBAX® brand nylon block copolymer and 0.125 to 1.00 percent by weightof a triallyl cyanurate or triallyl isocyanurate, irradiated by electronbeam at total fluences of 0.5 to 7 megarads (comparative examples at 0.0megarads also being included in Table 4).

It is believed that the data in Tables 1 through 4 demonstrate that amedical device 10 of the present invention, incorporating a balloon 18comprising an irradiated mixture of a polyamide elastomer and at leastone additional cross-linking reactant as defined herein, possessessignificant advantages over prior medical devices incorporating balloonsmade of other materials. The present invention thus provides a medicaldevice 10 which is particularly useful for dilating a narrowing orobstruction in a vessel or lumen in a patient, and for deploying a stentacross the site of such a narrowing or obstruction to prevent itsrestenosis. The balloon 18 of the device 10 of the present invention hasa generally improved combination of strength (for example, greatertensile strength, burst pressure and/or puncture resistance) andcompliance in comparison to balloons in prior devices for thesepurposes. Gelling during the steps leading to manufacture of the balloon18, if present, is limited to an acceptable level. The balloon 18 of themedical device 10 of the present invention is made from materials whichmeet a variety of desirable processing criteria, including thermalstability, non-toxicity, non-volatility, high boiling point (preferably,solid at room temperature), high flash point, insensitivity to moistureand commercial availability.

TABLE 1 Nomi- Nom- nal Com- Mean Parison inal Balloon pli- Burst FrenchVendor Avg. Pres- Dia- ance Avg. Std Double Dia- size Material Mat'l.Mat'l. Tensile Std. Elon- Std. sure meter (mm/ Burst Dev Wall meter(O.D.) Desc. Lot # Lot # Formulation (lb.) Dev gation Dev (atm) Mrad(mm) atm) (atm) (atm) (ln) (mm) 4.7 R & D S66246 P136575 7233SAO1 10.5151.20 7.69 1.095 3 5 6.00 0.14 10.1 0.78 0.00125 6.75 1102 w/2% XL 4.7 R& D S66246 P136575 7233SAO1 9.706 1.11 7.241 0.916 3 7 6.00 0.12 9.970.78 0.00125 6.8 1102 w/2% XL 6.1 R & D S66246 P136573 7233SAO1 17.5751.218 7.765 0.594 5 5.00 1102 w/2% XL 6.1 R & D S66246 P136573 7233SAO118.725 1.48 8.943 0.672 7 5.00 1102 w/2% XL 3 4 R & D S68043 P1374207233SAO1 12.054 0.537 12.561 0.697 0 4.00 1137 w/3% XL 3.4 R & D S68043P137420 7233SAO1 10.5 0.786 7.84 0.829 2.5 4.00 1137 w/3% XL 3.4 R & DS68043 P137420 7233SAO1 10.6 0.757 7.60 0.609 11.5 4 4.00 0.04 25 1.630.002 3.36 1137 w/3% XL 3.4 R & D S68043 P137420 7233SAO1 10.6 0.7577.60 0.509 11 4 4.00 0.036 26.2 1.58 0.002 3.38 1137 w/3% XL 5.5 R & DS68043 P137423 7233SAO1 21.508 1.748 11.841 0.721 0 6.00 0.21 13.2 0.40.00175 7.94 1137 w/3% XL 5.5 R & D S68043 P137423 7233SAO1 20.549 1.6487.65 0.831 3 6.00 0.09 14.8 1 0.00225 6.54 1137 w/3% XL 5.5 R & D S68043P137423 7233SAO1 18.948 1.055 7.89 0.733 5 6.00 0.083 15.4 0.9 0.002256.5 1137 w/3% XL 5.5 R & D S68043 P137423 7233SAO1 20.072 1.185 7.500.658 8 6.00 0.088 15.39 1.18 0.00225 8.51 1137 w/3% XL 5.5 R & D S68043P138587 7233SAO1 28.39 2.143 13.938 1.113 3 0 6.00 0.215 15.6 0.5 0.0029.07 1137 w/3% XL 5.5 R & D S68043 P138587 7233SAO1 27.893 2.179 10.3920.952 7 3 6.00 0.085 18.2 2.8 0.0025 7.08 1137 w/3% XL 5.5 R & D S88043P138587 7233SAO1 25.765 1.73 9.237 0.727 8 5 6.00 0.075 18.5 1.95 0.00256.58 1137 w/3% XL 5.5 R & D S88043 P138587 7233SAO1 25.766 1.73 9.2370.727 8 5 6.00 0.069 19.05 1.17 0.0025 6.83 1137 w/3% XL 5.5 R & DS88043 P138587 7233SAO1 25.766 1.73 9.237 0.727 7 5 6.00 0.052 20.29 1.30.0025 8.81 1137 w/3% XL 5.5 R & D S88043 P138587 7233SAO1 26.842 2.3859.319 0.947 9 7 6.00 0.079 19.8 0.96 0.0025 6.95 1137 w/3% XL 5.5 R & DS68043 P138587 7233SAO1 22.977 2.01 7.533 0.753 15 5.00 1137 w/3% XL 5.5R & D S68043 P138587 7233SAO1 22.311 1.69 6.751 0.564 25 6.00 1137 w/3%XL 5.5 R & D S68043 P138587 7233SAO1 19.907 0.976 5.213 0.284 50 6.001137 w/3% XL 5.5 R & D S68043 P138587 7233SAO1 19.08 1.392 4.669 0.42575 6.00 1137 w/3% XL 5.5 R & D S68043 P138587 7233SAO1 17.714 0.8173.468 0.228 100 6.00 1137 w/3% XL 5.5 R & D S88541 P138614 10% 26.6391.379 12.414 0.735 0 6.00 1138 PA12/86.5% 7233SAO1/ 3% XL 5.5 R & DS68541 P138614 10% 22.232 0.477 7.97 0.497 3 6.00 1138 PA12/86.5%7233SAO1/ 3% XL 5.5 R & D S68541 P138614 10% 22.612 1.001 8.273 0.552 105 6.00 0.065 17.6 2.5 0.003 6.31 1138 PA12/86.5% 7233SAO1/ 3% XL 5.5 R &D S68541 P138614 10% 20.807 1.229 7.08 0.691 7 6.00 1138 PA12/86.5%7233SAO1/ 3% XL 5.5 R & D S68541 P138614 10% 18.537 1.109 5.882 0.432 156.00 1138 PA12/86.5% 7233SAO1/ 3% XL 5.5 R & D S68541 P138614 10% 18.441.286 4.872 0.544 25 6.00 1138 PA12/86.5% 7233SAO1/ 3% XL 5.5 R & DS68541 P138614 10% 13.388 0.804 1.585 1.332 100 6.00 1138 PA12/86.5%7233SAO1/ 3% XL 5.5 R & D S69481 P138591 7233SAO1 19.372 0.29 8.6350.191 3 3 6.00 0.19 15.73 0.451 0.002 8.74 1157 w/10% PA12 5.5 R & DS69481 P138591 7233SAO1 18.732 0.348 8.082 0.326 3 5 6.00 0.253 15.70.48 0.00225 9.01 1157 w/10% PA12 5.5 R & D S69481 P138591 7223SAO118.831 1.203 8.358 0.657 3 7 6.00 0.173 14.81 0.528 0.0015 8.43 1157w/10% PA12 5.5 R & D S69481 P138591 7233SAO1 19.939 0.779 8.294 0.459 315 6.00 0.189 13.23 0.483 0.0015 8.35 1157 w/10% PA12 5.5 R & D S69481P138591 7233SAO1 17.404 0.71 7.569 0.491 25 6.00 1157 w/10% PA12 5.5 R &D S69481 P138591 7233SAO1 15.892 0.868 5.476 0.395 50 6.00 1157 w/10%PA12 5.5 R & D S69481 P138591 7233SAO1 12.152 0.641 1.447 2.057 100 6.001157 w/10% PA12 5.5 40080 S64330 P138669 Nylon 6/8 38.336 2.184 11.5770.773 0 6.00 0% XL

TABLE 2 Parison French Vendor Avg. size Material Mat'l. Mat'l. Tensile(O.D.) Desc. Lot # Lot # Formulation (lb.) Std. Dev Elongation 5.5 40140S68802 P138661 Nylon 12 0% XL 22.116 0.84 7.841 5.8 R & D S66246 P1390147233SAO1 w/2% XL 27.313 0.701 13.113 1102 5.8 R & D S66246 P1390147233SAO1 w/2% XL 25.482 1.427 9.972 1102 5.8 R & D S66246 P1390147233SAO1 w/2% XL 24.93 1.547 9.32 1102 5.8 R & D S66246 P139014 7233SAO1w/2% XL 24.93 1.547 9.32 1102 5.8 R & D S66246 P139014 7233SAO1 w/2% XL24.93 1.547 9.32 1102 5.8 R & D S66246 P139014 7233SAO1 w/2% XL 24.931.547 9.32 1102 5.8 R & D S66246 P139014 7233SAO1 w/2% XL 24.93 1.5479.32 1102 5.8 R & D S66246 P139014 7233SAO1 w/2% XL 23.226 1.488 8.3711102 5.8 R & D S66246 P139014 7233SAO1 w/2% XL 20.757 1.604 6.963 11025.8 R & D S66246 P139014 7233SAO1 w/2% XL 20.75 0.951 6.84 1102 5.8 R &D S66246 P139014 7233SAO1 w/2% XL 19.3 0.86 5.645 1102 5.8 R & D S88246P139014 7233SAO1 w/2% XL 16.612 0.876 3.792 1102 5.8 R & D S68541/P138892 10% PA12/86.5% 33.929 1.75 15.984 1138/ S5967 7233SAO1/3% XL41130 5.8 R & D S68541/ P138892 10% PA12/86.5% 25.412 2.583 9.424 1138/S5967 7233SAO1/3% XL 41130 5.8 R & D S88541/ P138892 10% PA12/86.5%24.227 2.081 9.287 1138/ S5967 7233SAO/3% XL 41130 5.8 R & D S88541/P138892 10% PA12/86.5% 23.907 1.344 8.827 1138/ S5967 7233SAO1/3% XL41130 5.8 R & D S68541/ P138892 10% PA12/86.5% 22.803 1.748 8.245 1138/S5967 7233SAO1/3% XL 41130 5.8 R & D S88541/ P138892 10% PA12/86.5%22.024 0.752 8.821 1138/ S5967 7233SAO1/3% XL 41130 5.5 41130 S59677P138180 7233SNO1 5.5 41130 S59877 P138180 7233SNO1 19.581 0.735 12.3585.5 41130 S59677 P138180 7233SNO1 18.986 0.494 12.095 5.5 41130 S59677P138180 7233SNO1 17.168 0.996 10.328 5.5 41130 S59677 P138180 7233SNO115.888 0.918 9.156 5.5 41130 S59677 P138180 7233SNO1 14.582 0.473 7.6585.5 41130 S59677 P138180 7233SNO1 13.545 0.762 6.279 5.5 41130 S59677P138180 7233SNO1 12.192 0.662 5.581 6.2 R & D S68043 P137426 7233SAO1w/3% XL 30.464 1.361 13.559 1137 6.2 R & D S68043 P137426 7233SAO1 w/3%XL 25.773 1.341 8.577 1137 6.2 R & D S68043 P137426 7233SAO1 w/3% XL25.235 2.492 7.158 1137 6.2 R & D S68043 P137426 7233SAO1 w/3% XL 24.4051.355 6.753 1137 6.2 R & D S68042 P137432 7233SAO1 W/10% 27.116 1.65910.449 1138 PA12 w/3% XL 6.2 R & D S68042 P137432 7233SAO1 W/10% 26.4951.809 6.753 1138 PA12 w/3% XL 6.2 R & D S68042 P137432 7233SAO1 W/10%24.552 1.685 6.062 1138 PA12 w/3% XL 6.2 R & D S68042 P137432 7233SAO1W/10% 23.852 1.925 5.382 1138 PA12 w/3% XL 6.2 R & D S66758/ P1374336333SNO1 + 7233SAO1 29.92 2.724 16.854 1138 S6804 W/10% PA12 w/3% XL 6.2R & D S66758/ P137433 6333SNO1 + 7233SAO1 25.198 2.647 9.614 1138 S6804W/10% PA12 w/3% XL 6.2 R & D S66768/ P137433 6333SNO1 + 7233SAO1 23.2443.8206 9.315 1138 S6804 W/10% PA12 w/3% XL Parison Nominal Mean FrenchNominal Balloon Com- Avg. Double Burst size Pressure Diameter plianceBurst Std Dev Wall Diameter (O.D.) Std. Dev (atm) Mrad (mm) (mm/atm)(atm) (atm) (ln) (mm) 5.5 0.459 4 0 6.00 0.0861 20.25 0.661 0.002 7.595.8 0.426 0 6.00 5 8 0.638 5 3 6.00 0.064 18.5 1.46 0.0025 7.27 5.80.738 7 5 6.00 0.098 18.15 1.13 0.0025 7.01 5.8 0.738 6 5 6.00 0.09318.15 1.13 0.0025 7.03 5 8 0.738 6 5 6.00 0.096 19.07 0.807 0.0025 7.335.8 0.738 6.5 5 6.00 0.053 17.72 0.982 0.0025 6.66 5.8 0.738 6 5 6.000.063 18.79 1.18 0.0025 7.18 5.8 0.501 7 7 6.00 0.08 18.25 1.28 0.00256.9 5.8 0.625 8 15 6.00 0.052 17.4 1.69 0.0025 6.51 5.8 0.35 8 25 6.000.0497 15.53 2.33 0.0025 6.23 5.8 0.357 50 6.00 5.8 0.175 100 6.00 5.80.822 0 6.00 5.8 0.851 3 6.00 5.8 0.649 5 6.00 5.8 0.524 7 6.00 5.80.653 15 6.00 5.8 0.385 25 6.00 5.5 0 6.00 0.197 15.4 0.45 0.002 8.7 5.50.719 5 6.00 0.24 13.1 0.74 0.002 8.3 5.5 0.478 15 6.00 0.24 12 0.030.002 8.5 5.5 0.926 25 6.00 5.5 0.483 40 6.00 5.5 0.207 50 6.00 0.17310.3 0.6 0.002 7.42 5.5 0.5 70 6.00 5.5 0.216 100 6.00 0.12 11.1 0.0050.002 6.97 6.2 0.595 0 6.00 6.2 0.414 3 6.00 6.2 0.835 5 6.00 6.2 0.4096 6.00 6.2 0.656 0 6.00 6.2 0.504 3 6.00 6.2 0.491 5 6.00 6.2 0.625 66.00 6.2 1.265 0 6.00 6.2 1.177 3 6.00 6.2 1.444 5 6.00

TABLE 3 Nom- inal Nom- Bal- Com- Mean Parison inal loon pli- Dou- BurstFrench Vendor Avg. Pres- Dia- ance Avg. Std ble Dia- size MaterialMat'l. Mat'l. Tensile Std. Elon- Std. sure meter (mm/ Burst Dev Wallmeter (O.D.) Desc. Lot # Lot # Formulation (lb.) Dev gation Dev (atm)Mrad (mm) atm) (atm) (atm) (ln) (mm) 6.2 R & D S66758/ P1374336333SNO1 + 25.933 3.108 9.646 0.9182 6 6.00 1138 S6804 7233SAO1 W/10%PA12 w/3% XL 6.2 R & D S66758/ P137433 6333SNO1 + 25.597 3.0238 9.1891.239 7 6.00 1138 S6804 7233SA01 W/10% PA12 w/3% XL 6.2 R & D S66758/P137433 6333SNO1 + 25.664 1.554 10.01 0.616 8 6.00 1138 S6804 7233SAO1W/10% PA12 w/3% XL 6.9 R & D S68541 P138860 7233SAO1 32.284 2.73 12.7791.27 0 6.00 1138 W/10% PA12 w/3% XL 6.9 R & D S68541 P138860 7233SAO128.813 2.874 7.325 0.833 3 6.00 1138 W/10% PA12 w/3% XL 6.9 R & D S68541P138860 7233SAO1 27.19 1.399 6.899 0.38 5 6.00 1138 W/10% PA12 w/3% XL6.9 R & D S68541 P138860 7233SAO1 28.04 1.707 6.813 0.441 7 6.00 1138W/10% PA12 w/3% XL 6.9 R & D S68541 P138860 7233SAO1 26.263 2.33 5.9180.599 15 6.00 1138 W/10% PA12 w/3% XL 7.6 R & D S68541 P138885 7233SAO133.75 3.593 11.861 1.253 0 10.00 1138 W/10% PA12 w/3% XL 7.6 R & DS68541 P138885 7233SAO1 31.242 1.784 6.799 0.4 3 10.00 1138 W/10% PA12w/3% XL 7.6 R & D S68541 P138885 7233SAO1 30.434 2.437 6.198 0.554 510.00 1138 W/10% PA12 w/3% XL 7.6 R & D S68541 P138885 7233SAO1 28.0150.95 6.141 0.24 7 10.00 1138 W/10% PA12 w/3% XL 7.6 R & D S68541 P1388857233SAO1 26.751 1.417 5.087 0.337 15 10.00 1138 W/10% PA12 w/3% XL 7.6 R& D S68541 P138885 7233SAO1 25.218 1.368 4.385 0.408 25 10.00 1138 W/10%PA12 w/3% XL 8.5 R & D S88541 P138886 7233SAO1 49.668 2.033 14.768 0.6730 12.00 1138 W/10% PA12 w/3% XL 8.5 R & D S68541 P138866 7233SAO1 36.8252.034 6.604 0.348 5 12.00 1138 W/10% PA12 w/3% XL 8.5 R & D S68541P138886 7233SAO1 37.511 2.643 6.744 0.598 7 12.00 1138 W/10% PA12 w/3%XL 8.5 R & D S68541 P138886 7233SAO1 33.328 1.486 6.209 0.536 15 12.001138 W/10% PA12 w/3% XL 8.5 R & D S68541 P138886 7233SAO1 31.665 0.8135.576 0.244 25 12.00 1138 W/10% PA12 w/3% XL 9.9 R & D S68541 P1388877233SAO1 67 5.628 16.82 1.259 0 12.00 1138 W/10% PA12 w/3% XL 9.9 R & DS68541 P138887 7233SAO1 52.887 2.465 8.570 0.642 3 14.00 1138 W/10% PA12w/3% XL 9.9 R & D S68541 P138887 7233SAO1 59.914 1.943 9.888 0.685 514.00 1138 W/10% PA12 w/3% XL 9.9 R & D S68541 P138887 7233SAO1 63.9754.47 10.121 0.734 7 14.00 1138 W/10% PA12 w/3% XL 9.9 R & D S68541P138887 7233SAO1 58.594 1.964 8.338 0.278 15 14.00 1138 W/10% PA12 w/3%XL 9.9 R & D S68541 P138887 7233SAO1 51.635 1.417 6.892 0.321 25 14.001138 W/10% PA12 w/3% XL

TABLE 4 Parison Vendor Nominal Compli- Mean French Mat'l. Balloon anceAve Std Double Burst size Material Lot Mat'l. Diameter mm/ Burst Dev RBPWall Diameter (O.D.) Desc. # Lot # Formulation (Mrad) (mm) atm (atm)(atm) (atm) (ln) (mm) 6.1 R & D 1202 S70350 P139685 7233SAO1 0 6.000.178 17.68 0.459 15.29 0.0025 8.76 w/⅛% XL 6.1 R & D 1202 S70350P139685 7233SAO1 0.5 6.00 0.194 17.08 0.22 15.93 0.0025 9.05 w/⅛% XL 6.1R & D 1202 S70350 P139685 7233SAO1 1 6.00 0.168 16.98 0.025 18.85 0.00258.77 w/⅛% XL 6.1 R & D 1202 S70350 P139685 7233SAO1 2 6.00 0.167 16.370.483 13.86 0.0025 8.35 w/⅛% XL 6.1 R & D 1202 S70350 P139685 7233SAO1 36.00 0.174 16.96 0.081 16.54 0.0025 8.84 w/⅛% XL 6.1 R & D 1202 S70350P139685 7233SAO1 5 6.00 0.17 16.13 0.303 14.55 0.0025 8.38 w/⅛% XL 6.1 R& D 1202 S70350 P139685 7233SAO1 7 6.00 0.146 15.91 0.297 14.37 0.00257.94 W/⅛% XL AVERAGES 0.1739 16.73 0.267 15.34 0.0025 8.58 6.1 R & D1203 S70351 P139687 7233SAO1 0 6.00 0.198 17.24 0.603 14.1 0.0025 9.00w/¼% XL 6.1 R & D 1203 S70351 P139687 7233SAO1 0.5 6.00 0.188 17.840.324 16.15 0.0025 8.9 w/¼% XL 6.1 R & D 1203 S70351 P139667 7233SAO1 16.00 0.18 17.59 0.45 15.24 0.0025 8.8 w/¼% XL 6.1 R & D 1203 S70351P139687 7233SAO1 2 6.00 0.129 16.98 0.054 18.68 0.0025 7.78 w/¼% XL 6.1R & D 1203 S70351 P139687 7233SAO1 3 6.00 0.131 16.98 0.037 16.77 0.00257.88 w/¼% XL 6.1 R & D 1203 S70351 P139687 7233SAO1 5 6.00 0.127 16.770.373 14.82 0.0025 7.8 w/¼% XL 6.1 R &D 1203 S70351 P139687 7233SAO1 76.00 0.117 16.11 0.147 15.37 0.0025 7.53 w/¼% XL AVERAGES 0.1529 17.070.284 15.59 0.0025 8.21 6.1 R & D 1137 S70349 P139688 7233SAO1 0 6.000.154 16.88 0.333 15.08 0.0025 8.20 w/½% XL 6.1 R & D 1137 S70349P139686 7233SAO1 0.5 6.00 0.15 18.19 0.417 16.02 0.0025 9.07 w/½% XL 6.1R & D 1137 S70349 P139668 7233SAO1 1 6.00 0.153 18.09 0.548 15.24 0.00258.2 w/½% XL 6.1 R & D 1137 S70349 P139688 7233SAO1 2 6.00 0.14 17.550.463 15.15 0.0025 8.06 w/½% XL 6.1 R & D 1137 S70349 P139688 7233SAO1 36.00 0.136 17 0.029 16.86 0.0025 8.06 w/½% XL 6.1 R & D 1137 S70349P159688 7233SAO1 5 6.00 0.108 16.75 0.465 14.33 0.0025 7.43 w/½% XL 6.1R & D 1137 S70349 P139688 7233SAO1 7 6.00 0.095 16.02 0.125 15.37 0.00257.16 w/½% XL AVERAGES 0.1337 17.21 0.34 15.44 0.0025 8.03 6.1 R & D 1102S70348 139689 7233SAO1 0 6.00 0.168 16.98 0.465 14.56 0.0025 7.62 w/1%XL 6.1 R & D 1102 S70348 139689 7233SAO1 0.5 6.00 0.107 18.12 0.30816.51 0.0025 7.44 w/1% XL 6.1 R & D 1102 S70348 139889 7Z33SAO1 1 6.000.113 18.04 0.448 15.71 0.0025 7.42 w/1% XL 6.1 R & D 1102 S70348 1396897233SAO1 2 6.00 0.108 17.95 0.305 16.36 0.0025 7.37 w/1% XL 6.1 R & D1102 S70348 139689 7233SAO1 3 6.00 0.11 17.94 0.298 16.38 0.0025 7.36w/1% XL 6.1 R & D 1102 S70348 139689 7233SAO1 5 6.00 0.098 17.64 0.47915.15 0.0025 7.03 w/1% XL 6.1 R & D 1102 S70348 139689 7233SAO1 7 6.000.081 17.11 0.602 13.98 0.0025 6.90 w/1% XL AVERAGES 0.112 17.68 0.41515.52 0.0025 7.31

By way of non-limiting example, a particularly preferred process forforming a medical device balloon includes the following steps. First, ablend of PEBAX® 7233 and 1 percent by weight triallyl isocyanurate (asthe additional cross-linking reactant) is extruded in the form of atubing of desired diameter. The extruded tubing blend is then exposed to3 megarads of irradiation via electron beam. The ends of the tubing aredrawn or stretched to a reduced diameter, while a central portionbetween the ends of the tubing is left undrawn or unstretched, thiscentral portion of the tubing being the portion from which the balloon18 is blown. The tubing is then introduced into a mold and preliminarilyheated to about 135° F. to about 150° F., then subjected to a blowpressure of about 350 psi to about 650 psi and a blow temperature ofabout 200° F. to about 250° F. The temperature of the mold is thenraised by about 30° F. for about 30 sec to about 60 sec, to further setor cure the blown material. The mold is cooled and the blown materialremoved from the mold. The central, undrawn portion constitutes theballoon 18, and is cut from the tubing and mounted to the catheter shaft11 in a suitable manner. The times, pressures and temperatures of thisnon-limiting example depend, of course, upon the thickness and innerdiameter of the partially drawn tubing; those skilled in the art ofmedical balloon manufacture should be well capable of varying theseconditions to yield a suitable balloon from any particular initialmaterial blend.

Further Implementation of the Principles of the Disclosed Invention.

The principle of the present invention, that is, changing the durometerof only part of a suitably composed article by selectively exposing thearticle to cross-linking irradiation, can be applied to obtain a varietyof useful medical devices. The article preferably comprises anirradiation cross-linkable mixture of a polyamide elastomer and at leastone additional cross-linking reactant, and more preferably comprises oneof the materials disclosed above. Many of the materials disclosed inInternational Applications WO 98/55161 and WO 98/15199, as well as inU.S. Pat. Nos. 5,900,444 (Zamore, May 4, 1999), No. 5,993,415 (O'Neil etal., Nov. 30, 1999) and No. 5,998,551 (O'Neil et al., Dec. 7, 1999) mayalso be useful for this purpose, depending upon whether the resultingmedical device incorporating any particular material is in fact usefulfor its intended purpose. The entirety of all of these disclosures areexpressly incorporated by reference herein. It is believed that thoseskilled in the art of catheter design and manufacture can readilydetermine the usefulness of the materials identified in thesedisclosures without undue experimentation, most readily by simpletrial-and-error.

As indicated above, the material mixtures of the Examples were firstformed into tubing 26 and irradiated before any balloon was blown fromthem. Accordingly, those mixtures of the Examples in Tables 1 through 4which include the at least one additional cross-linking reactantconstitute Examples of this further implementation of the presentinvention. The mixtures including nylon are probably particularlypreferred in the practice of this further implementation of the presentinvention.

In any event, exposing only a part of an article to irradiation, orexposing different parts of an article to different amounts ofirradiation, gives the different parts of the article different degreesof cross-linking, and therefore different durometers.

A wide range of medical devices having a varying durometer can bemanufactured in accordance with the principles of the present invention.For example, while the present invention is useful in forming balloon,diagnostic and infusion catheters of a variety of diameters, the presentinvention is particularly useful in forming infusion catheters having anoutside diameter below about 1 mm. Such catheters are sometimes known as“microcatheters” and are presently very popular products. They require avariety of functional characteristics. Microcatheters need to be strongenough to accommodate manipulation during introduction into and removalfrom a patient and to accommodate adequate pressure injection whendeployed in a patient. At the same time, microcatheters need to have alow coefficient of friction (to allow the passage therein of micro-sizedwire guides) and need to be small enough to allow their placement insmall, distal vessels in the patient, yet still need to be soft enoughto be able to flow directly into very tortuous paths within the patient.

Two known devices which meet these different needs are made fromcombinations of different materials in order to meet those needs. Oneknown device is disclosed in U.S. Pat. No. 4,739,768 (Engelson, Apr. 26,1988) and is believed marketed by Target Therapeutics (Los Angeles,Calif.) under the name “Tracker.” The device disclosed in the Engelsonpatent comprises two or three small bore polyethylene tubes, each havinga different hardness or durometer (hardest at the proximal end andsoftest at the distal end). The Engleson device also comprises an outersleeve that extends the full length of the catheter and beyond thedistal end of the distal-most inner tube. The outer sleeve ensures thatthe joints between the inner tubes of different durometer stay togetherduring use of the device and, as desired for microcatheters, providesthe device with a very soft and flexible distal tip. While the deviceachieves properties which have not previously been obtained with acatheter shaft composed of a single material, the device isunfortunately relatively complex.

Another known microcatheter which meets these different needs ismarketed by Cook Incorporated (Bloomington, Ind.) under the trademarkMicroFerret™. The Cook device comprises three separate polyethylenetubes of different durometer that are butt welded together to yield acatheter having varying degrees of stiffness along its length. The soft,flexible distal tip of the catheter resists kinking when advancedthrough tortuous vascular anatomy, yet the proximal rigid and mediumshaft stiffnesses give the catheter high pushability, that is, thecatheter is readily advanced within the patient. Unfortunately, thesmall diameters of the tubes make the butt bonds or welds difficult toform, and the finished product has relatively abrupt changes ofstiffness along its length.

The drawbacks of the Engelson and Cook microcatheters arise, in part,because microcatheters generally require materials that have highmoduli, that is, materials in which the initial slope of the appliedforce versus the resulting elongation of the materials is high. Thisproperty of high modulus is simply not possessed by conventionalmaterials which are desirably soft. Thus, the prior devices havenecessarily required a plurality of parts of different durometer inorder to function well.

The present invention, however, provides a solution to this problem,since the amount of cross-linking along the catheter (and thus thedurometer along the catheter) can be selected by varying the amount ofirradiation to which the material of the catheter is exposed. The partsof the catheter that need to remain flexible or compliant are shieldedby a metallic or other shield, while the parts which need to bestiffened are exposed to the irradiation source. The stiffness of thecatheter can further be varied by forming the catheter via a “bump”extrusion process, wherein the wall thickness is increased in areasrequiring more stiffness, and decreased in areas requiring moreflexibility. The yield strength of the cross-linked material can beenhanced by stressing the material at an elevated temperature(longitudinally, circumferentially or both), even so far as the limitsof the molecular bonds.

Such a catheter, and the method for forming it, are shown in FIG. 4.More particularly, in its simplest form a medical device 110 accordingto the present invention comprises a unitarily and continuously formedportion 108 having a varying durometer. The unitarily and continuouslyformed portion 108 preferably comprises at least a first unitarily andcontinuously formed part 102 and a second uniformly and continuouslyformed part 104, the first and second parts 102 and 104 having differentdurometers. The portion 108 preferably also comprises a transition zone105 of continuously varying durometer connecting the first and secondparts 102 and 104, the transition zone 105 being unitarily andcontinuously formed with the first and second parts 102 and 104 of theportion 108. In FIG. 4, the unitarily and continuously formed portion108 is shown as a tubular portion 106. More particularly, the tubularportion 106 comprises and is configured as a catheter shaft 111. Thefirst part 102 of the unitarily and continuously formed portion 108constitutes a first (for example, a distal) catheter shaft segment 178comprised in the catheter shaft 111, while the second part of theportion 108 constitutes a second (for example, a proximal) cathetershaft segment 180 comprised in the catheter shaft 111. The first andsecond catheter shaft segments 178 and 180 are unitarily andcontinuously formed with one another and have different durometers.

The first and second catheter shaft segments 178 and 180 are physicallyconfigured as desired, via molding, extrusion or other conventionalprocesses. As shown, if the first catheter shaft segment 178 is shieldedfrom a radiation source 200 by a tapered shield 196 while the secondcatheter shaft segment 180 is cross-linked by exposure to the radiationsource, the first catheter shaft segment 178 will remain soft while thedurometer of the second catheter shaft segment 180 is increased. Thecatheter shaft 111 is thereby given a varying durometer suitable for usein an infusion catheter, particularly in an infusion microcatheterhaving an outside diameter below about 1 mm. The resulting medicaldevice 110 can include a radiopaque band (not shown) near its distalend, as an aid to positioning the device in a patient.

The transition zone 105 extends between the first and second cathetersegments 178 and 180, and lies beneath the taper 202 of the taperedshield 196. The length of the taper 202 of the shield 196 establishesthe length of the transition zone 105. Additional segments of differentdurometer and/or additional transition zones can be provided by simplyincluding additional tapers on the shield 196. Alternatively, theadditional segments or zones can be provided by moving the shield 196with respect to the catheter shaft 111, and exposing the catheter shaft111 to irradiation one or more additional times. The arrow 198 indicatesthe relative movement of the catheter shaft 111 and the shield 196 onthe one hand, and the radiation source 200 on the other, duringirradiation cross-linking.

If for some reason it is desired that the transition zone 105 besubstantially eliminated, the taper 202 can be omitted from the shield196 and a straight edge provided on the shield 196 in its place. Anytransition between the first and second catheter shaft segments 178 and180, or other unitarily and continuously formed first and second parts102 and 104 of the portion 108, would then be limited to cross-linkingresulting from diffraction of radiation passing the edge of the shield196.

The exact opposite result can be readily achieved, that is, thedurometer of the unitarily and continuously formed portion 108 canreadily be varied continuously along the length of the portion 108. Sucha result is the equivalent of having the transition zone 105 extend theentire longitudinal length of the portion 108 and could be obtained byemploying a shield (not shown) whose taper 202 was as long as theportion 108 itself.

The catheter shaft 111 can be modified to make it useful for otherpurposes, for example, for use in a catheter needle set. Conventionalcatheter needle sets employ a catheter introduced into a patientdirectly on a needle. Such sets are typically used for introducing ashort catheter into an abscess for drainage, for access to a bile ductor for other well-known purposes. In conventional sets, the tip of thecatheter portion is made from a harder durometer material which isbonded to the distal end of a softer catheter shaft. A step or ledge isformed on the inside of the harder catheter tip portion near its distalend, and a ring or collar is provided on the needle which is capable ofabutting or engaging the step or ledge. Such an arrangement preventsmovement or slippage (“accordioning”) of the catheter along the needleduring passage of the catheter and needle through tissue of the patient.Particularly in smaller diameters, attachment of the harder catheter tipto the catheter shaft may be problematic.

The present invention solves this problem by permitting only a segmentof the catheter shaft to be hardened. Thus, as shown in FIG. 5, one ofthe first and second catheter shaft segments 178 and 180 (for example,the first catheter shaft segment 178) can comprise a catheter tip 184.The other segment (for example, the second catheter shaft segment 180)then comprises a catheter body 186. Either the catheter tip 184 or thecatheter body 186 can have the greater durometer. In the catheter needleset shown in FIG. 5, the catheter tip 184 has the greater durometer byhaving been exposed to a greater total fluence of irradiation than thecatheter body 186. This could be achieved, for example, by disposing theshield 196 in a position opposite to that shown in FIG. 4, shielding thecatheter body 186 while permitting the catheter tip 184 to be exposed tothe radiation source 200. It should be recalled, however, that in othercatheter structures it is often preferred that the catheter body 186have a greater durometer than the catheter tip 184.

The catheter tip 184 is preferably configured for use in a catheterneedle set. Accordingly, the catheter tip 184 includes a distal end 190,and a step or ledge 188 formed in the catheter tip 184 near its distalend 190. The medical device 110 then further comprises a needle 192receivable in the catheter shaft 111 (in particular, in the catheterbody 186). The needle 192 bears on it a ring, a collar, an enlargementor the like 194 which is engageable with or abuttable against the stepor ledge 188 in the catheter tip 184. As in conventional catheter needlesets, such engagement or abutment prevents movement or slippage of thecatheter shaft 111 with respect to the needle 192 during its passagethrough patient tissue. Advantageously, however, the resulting catheter111 is of unitary, single piece construction, such that the problems ofattaching a discrete tip to a catheter shaft are avoided.

Other modifications of the tubular portion 106 of the unitarily andcontinuously formed portion 108 can make the medical device 110 of thepresent invention useful for other purposes. For example, a variety ofcatheters are used for drainage of abscesses or other locations in apatient, for direct feeding of a patient into the patient's stomach(gastrostomy) or the like. Many of these catheters use an anchoringstructure (such as a malecot, pigtail, loop or the like) to keep thecatheter anchored in the stomach or cavity in which it is placed. Suchcatheters are considered indwelling, that is, they remain in the patientfor an extended period of time. It is therefore important to patientcomfort that such catheters be soft and pliable. Unfortunately, astiffer, springier anchor is much more effective at keeping the cathetertip in place than the desired softer, more pliable one. The presentinvention solves this drawback by providing a medical device 110 inwhich the anchor structure of a catheter or the like has a relativelyhigher durometer than the balance of the catheter. The resulting device110 has an anchor structure which is relatively stiff and springy, suchthat it is retained well in the patient, yet which is relatively softand pliable along its shaft, thereby making it more comfortable for thepatient.

Thus, as shown in FIGS. 6 through 8, the medical device 110 of thepresent invention can comprise a unitarily and continuously formedportion 108 which comprises a tubular portion 106 and an anchorstructure 170 unitarily and continuously formed with the tubular portion106, the anchor structure 170 and the tubular portion 106 havingdifferent durometers. Preferably, the durometer of the anchor structure170 is greater than the durometer of the tubular portion 106. The anchorstructure 170 can comprise a malecot 172 (FIG. 6), a pigtail 174 (FIG.7), a loop 176 (FIG. 8) or the like.

Of course, the catheter tip 184 disclosed above may comprise the anchorstructure 170, and in particular, any of the malecot 172, the pigtail174 or the loop 176.

Any number of other unitarily and continuously formed parts of differentdurometer can be included in the portion 108 of the medical device 110of the present invention. The specific shapes of such other parts wouldcorrespond to generally known shapes employed for generally knownpurposes, and the range of shapes need not be disclosed in detail here.Diagnostic catheters serve as specific examples of medical devicesincorporating shapes adapted to patient anatomy. Some of therequirements for diagnostic catheters include the strength to resistrupture or burst during the high pressure injection of radiopaque dyesinto patients, the ability to track well over a guide wire duringintroduction into a patient, a low coefficient of friction andthin-walled construction to allow the catheter to possess the largestpossible lumen within the limits of the outside diameter of thecatheter. Known materials for diagnostic catheters include polyethylene,polyamides, polyurethanes, polyvinylchloride and fluoropolymers. Whileeach of these materials may have one property which lends itself well touse in diagnostic catheters, each also has other properties whichresults in a compromise when employed in diagnostic catheters.

More particularly, polyethylene is soft and flexible, but is not verystrong. The softer, lower durometer grades of polyamides which aresuitable for vascular catheters are also not very strong. Polyurethanes,in contrast, may be very strong, but they have a high coefficient offriction. Polyvinylchloride is flexible but has a low yield strength.Fluoropolymers such as PTFE and FEP have low coefficients of friction,but are very stiff. Moreover, most diagnostic catheters, as well as sometherapeutic catheters, have curves or shapes at their distal ends whichaid the placement of the catheters in the patient by complying with theanatomy in which they are being used. In general, softer materials whichare typically suited to use in vascular catheters do not have good shaperetention; they are not springy enough to be very effective.

Catheters formed from the cross-linkable mixtures of polyamide andcross-linking reactant disclosed herein overcome these drawbacks. Theygenerally are flexible, strong and have low coefficients of friction,making them well suited for use in vascular catheters. Moreover, sinceparticular areas where desired shapes may be formed can be selectivelycross-linked and hardened, the catheters of the present invention shouldpossess improved retention of such desired shapes, and thereforeimproved function.

Of course, the materials disclosed for use in the present invention canbe used in combination with other materials to even greater functionaladvantage. As just one example, the materials of the present inventioncould be coextruded with a thin layer of TEFLON® or other lubriciousmaterial on its outside or inside diameter. This would add the propertyof vary low friction to a material that could be selectively stiffenedor hardened anywhere within a medical device where it would be ofadvantage.

The principles of the present invention cart also be successfullyapplied to balloon catheters, and even more advantageously in balloonmicrocatheters having an outside diameter less than about 1 mm. Ingeneral terms, as shown in FIG. 9 the medical device 110 of the presentinvention can comprise a unitarily and continuously formed portion 108of varying durometer, the portion 108 comprising a tubular portion 106and an inflatable balloon 118 unitarily and continuously formed with thetubular portion 106, the balloon 118 and the tubular portion 106 havingdifferent durometers. More particularly, the medical device 110 of thepresent invention can first comprise a catheter shaft 211 having anouter catheter shaft 114 and an inner catheter shaft 112 received in theouter catheter shaft 114, wherein the outer catheter shaft 114 comprisesthe unitarily and continuously formed portion 108 (without regard to itsparticular configuration). Advantageously, the outer catheter shaft 114of the medical device 110 comprises the tubular portion 106 of theportion 108. Preferably, the outer catheter shaft 114 further comprisesthe inflatable balloon 118, and is unitarily and continuously formedwith it. The inflatable balloon 118 has a distal end 119 secured to andsealed to the inner catheter shaft 112, such that the space between theinner and outer catheter shafts 112 and 114 defines a lumen 120 for thedelivery and removal of a pressurized inflation fluid to and from theinflatable balloon 118. The inner catheter shaft 112 can include a lumenformed therein (not shown) for receiving a guide wire therein.

The inflatable balloon 118 preferably has a durometer different fromthat of the outer catheter shaft 114 (or of the unitarily andcontinuously formed portion 108 or the tubular portion 106). Morepreferably, the inflatable balloon 118 comprises the preferred materialsdisclosed above for the discrete inflatable balloon 18. This is readilyachieved by allowing the portion 108, whatever its shape orconfiguration (such as the tubular portion 106) to comprise anirradiation cross-linkable mixture of a polyamide elastomer and at leastone additional cross-linking reactant. The portion 108 preferablycomprises at least the first and second parts 102 and 104 describedabove, unitarily and continuously formed with one another, and at leastone of the first and second parts 102 and 104 is exposed tocross-linking irradiation, such that they possess different durometers.The parts 102 and 104 can be exposed to different amounts ofcross-linking irradiation, or only one of the parts 102 or 104 can beexposed to cross-linking irradiation while the other is shielded. Inthis particular embodiment, the balloon 118 is preferably formed fromone of the parts 102 or 104, from the tubular part 106 or from the outercatheter shaft 114 by inflation after irradiation and cross-linking. Ofcourse, a separate balloon like the balloon 18 described above can beconnected to the outer and inner catheter shafts 114 and 112, and thedurometer of one of them (for example, the outer catheter shaft 114)varied in the manner described herein.

When constructed from the preferred materials disclosed herein, theinflatable balloon 118 possesses many of the advantageous propertiesdescribed above with respect to the inflatable balloon 18. Moreover, amedical device 110 having an inflatable balloon 118 unitarily andcontinuously formed with an outer catheter shaft 114 (or other elementdisclosed above) can readily be constructed in very small diameters,such as outside diameters below about 1 mm. The problems of preciselyforming a fluid inlet/outlet hole through the side of a plural lumencatheter shaft (enabling inflation of a conventional separate balloonmounted on the exterior of the shaft) and securing a separateconventional balloon to such a shaft over such a hole are affirmativelyavoided. The resulting medical device 110 possesses the outside diameterof a microcatheter and the superior balloon properties of theirradiation cross-linked materials, and is useful for performingangioplasty on very small vessels. In larger diameters, of course, theresulting medical device may be used to deploy a stent in the vascularsystem of a patient.

The particular process steps preferred for forming the medical device110 of the present invention have been described above and need not berepeated in detail. In general, the process steps of the presentinvention comprise forming the elements disclosed above, irradiatingthose portions desired to have durometers different from the durometersof the portions not irradiated and assembling the elements into themedical device 110 described

Similarly, the preferred materials which can be selectively cross-linkedin part, by selective irradiation, and employed to construct the medicaldevice 110 of the present invention, have been described in detailabove. While such details need not be repeated, it should be rememberedthat it is particularly preferred that the processes by which themedical device 110 are assembled, are carried out with an irradiationcross-linkable mixture comprising a nylon block copolymer includingpolyether blocks separated by polyamide blocks, about 3 percent byweight triallyl isocyanurate and about 10 percent by weight nylons

It is believed that the foregoing description clearly demonstrates thatthe medical device 110 of the present invention possesses significantadvantages over prior medical devices. In particular, the presentinvention provides a medical device 110 which is particularly useful fordeploying another medical device such as a stent into a patient or whichis itself to be deployed into a patient, for example, for establishing apassage or lumen in a patient, for expanding a narrowed or obstructedpassage or lumen in a patient or for introducing a therapeutic ordiagnostic fluid into a patient. The medical device 110 of the presentinvention advantageously retains a plurality of functions performed inprior devices by discrete or separate elements while eliminating suchdiscrete or separate elements. Moreover, the medical device 110 of thepresent invention can possess a continuous change in durometer, at leastin part, so as to eliminate the locations for kinking or deformationpresent in prior devices having discrete or separate elements ofdifferent durometer.

The details of the construction or composition of the various elementsof the medical devices 10 and 110 of the present invention not otherwisedisclosed are not believed to be critical to the achievement of theadvantages of the present invention, so long as the elements possess thestrength or mechanical properties needed for them to perform asdisclosed. The selection of any such details of construction arebelieved to be well within the ability of one of even rudimentary skillsin this area, in view of the present disclosure. For practical reasons,however, and particularly in the lower outside diameters, the medicaldevices 10 and 110 of the present invention should probably beconsidered to be single-use devices, rather than being reusable.

INDUSTRIAL APPLICABILITY

The present invention is useful for deploying another medical devicesuch as a stent into a patient, or which is itself to be deployed into apatient, for example, for establishing a passage or lumen in a patientfor expanding a narrowed or obstructed passage or lumen in a patient orfor introducing a therapeutic or diagnostic fluid into a patient, andtherefore finds applicability in human and veterinary medicine.

It is to be understood, however, that the above-described device ismerely an illustrative embodiment of the principles of this invention,and that other devices and methods for using them may be devised bythose skilled in the art, without departing from the spirit and scope ofthe invention. It is also to be understood that the invention isdirected to embodiments both comprising and consisting of the disclosedparts and process steps.

1. A process for assembling a medical device (110), the medical device(110) comprising a unitarily and continuously formed portion (108)having a varying durometer, and the process comprising: creating anirradiation cross-linkable mixture of a polyamide elastomer and at leastone additional cross-linking reactant; forming the mixture into aunitarily and continuously formed portion (108), placing a shield (196)of varying density between the unitarily and continuously formed portion(108) and a source of cross-linking irradiation; and exposing theunitarily and continuously formed portion (108), at least in part, tocross-linking irradiation, wherein forming is carried out so as to yielda unitarily and continuously formed portion (108) comprising at leastfirst and second parts (102 and 104) unitarily and continuously formedwith one another, and the exposing step comprises exposing at least oneof the first and second parts (102 or 104) to cross-linking irradiation,wherein the exposing step comprises exposing a unitarily andcontinuously formed transition zone (105) between the first and secondparts (102 and 104) to a continuously varying amount of cross-linkingirradiation.
 2. A process for assembling a medical device (110), themedical device (110) comprising a unitarily and continuously formedportion (108) having a varying durometer, and the process comprising:creating an irradiation cross-linkable mixture of a polyamide elastomerand at least one additional cross-linking reactant; forming the mixtureinto a unitarily and continuously formed portion (108); and exposing theunitarily and continuously formed portion (108), at least in part, tocross-linking irradiation, placing a shield (198) between the unitaryand continuously formed portion (108) and a source of cross-linkingirradiation, prior to the exposing step, wherein the shield (196) hasvarying density between the unitarily and continuously formed portion(108) and the source of cross-linking irradiation.
 3. A process forassembling a medical device (110), the medical device (110) comprising aunitarily and continuously formed portion (108) having a varyingdurometer, and the process comprising: creating an irradiationcross-linkable mixture of a polyamide elastomer and at least oneadditional cross-linking reactant; forming the mixture into a unitarilyand continuously formed portion (108); and exposing the unitarily andcontinuously formed portion (108), at least in part, to cross-linkingirradiation, the cross-linking reactant comprising an aromatic moleculecontaining at least two ring substituents, each of the ring substituentshaving labile hydrogens at a benzylic site therein, selected from theclass consisting of 1,3,5 triethyl benzene: 1,2,4 triethyl benzene; and1,3,5 triisopropyl benzene.